Basic fibroblast growth factor: Difference between revisions

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{{Infobox_gene}}
{{Infobox_gene}}
'''Basic fibroblast growth factor''', also known as '''bFGF''', '''FGF2''' or '''FGF-β''', is a member of the [[fibroblast growth factor]] family.<ref name="pmid9925931">{{cite journal | vauthors = Kim HS | title = Assignment1 of the human basic fibroblast growth factor gene FGF2 to chromosome 4 band q26 by radiation hybrid mapping | journal = Cytogenetics and Cell Genetics | volume = 83 | issue = 1-2 | pages = 73 | year = 1998 | pmid = 9925931 | doi = 10.1159/000015129 }}</ref>
'''FGF2''', also known as '''basic fibroblast growth factor''' (bFGF) and FGF-β, is a [[growth factor]] and [[signaling protein]] encoded by the ''FGF2'' [[gene]].<ref name="pmid1697263">{{cite journal | vauthors = Dionne CA, Crumley G, Bellot F, Kaplow JM, Searfoss G, Ruta M, Burgess WH, Jaye M, Schlessinger J | title = Cloning and expression of two distinct high-affinity receptors cross-reacting with acidic and basic fibroblast growth factors | journal = The EMBO Journal | volume = 9 | issue = 9 | pages = 2685–92 | date = September 1990 | pmid = 1697263 | pmc = 551973 | doi =  }}</ref><ref name="pmid9925931">{{cite journal | vauthors = Kim HS | title = Assignment1 of the human basic fibroblast growth factor gene FGF2 to chromosome 4 band q26 by radiation hybrid mapping | journal = Cytogenetics and Cell Genetics | volume = 83 | issue = 1-2 | pages = 73 | year = 1998 | pmid = 9925931 | doi = 10.1159/000015129 }}</ref> It is synthesized primarily as a 155 amino acid polypeptide, resulting in an 18 kDa protein.  However, there are four alternate start codons which provide N-terminal extensions of 41, 46, 55, or 133 amino acids, resulting in proteins of 22 kDa (196 aa total), 22.5 kDa (201 aa total), 24 kDa (210 aa total) and 34 kDa (288 aa total), respectively.<ref name="pmid 1785797">{{cite journal | vauthors = Florkiewicz RZ, Shibata F, Barankiewicz T, Baird A, Gonzalez AM, Florkiewicz E, Shah N | title = Basic fibroblast growth factor gene expression | journal = Annals of the New York Academy of Sciences | volume = 638 | issue = 1 | pages = 109–26 | date = December 1991 | pmid = 1785797 | doi = 10.1111/j.1749-6632.1991.tb49022.x }}</ref>  Generally, the 155 aa/18 kDa low molecular weight (LMW) form is considered cytoplasmic and can be secreted from the cell, whereas the high molecular weight (HMW) forms are directed to the cell's nucleus.<ref name="pmid 24780002">{{cite journal | vauthors = Coleman SJ, Bruce C, Chioni AM, Kocher HM, Grose RP | title = The ins and outs of fibroblast growth factor receptor signalling | journal = Clinical Science | volume = 127 | issue = 4 | pages = 217–31 | date = August 2014 | pmid = 24780002 | doi = 10.1042/CS20140100 | url = http://www.clinsci.org/content/127/4/217 }}</ref> 
 
[[Fibroblast growth factor]] protein was first purified in 1975, but soon afterwards others using  different conditions isolated basic FGF, Heparin-binding growth factor-2, and Endothelial cell growth factor-2.  Gene sequencing revealed that this group was in fact the same FGF2 protein and that it was a member of a [[Fibroblast_growth_factor|family of FGF]] proteins.<ref name="pmid 1785797"></ref><ref>{{cite journal | vauthors = Burgess WH, Maciag T | title = The heparin-binding (fibroblast) growth factor family of proteins | journal = Annual Review of Biochemistry | volume = 58 | pages = 575–606 | date = 1989 | pmid = 2549857 | doi = 10.1146/annurev.bi.58.070189.003043 }}</ref>  FGF2 binds to and exerts effects via specific [[Fibroblast_growth_factor_receptor|fibroblast growth factor receptor (FGFR)]] proteins which themselves constitute a family of closely related molecules.


== Function ==
== Function ==
In normal tissue, basic fibroblast growth factor is present in [[basement membrane]]s and in the [[endothelium|subendothelial]] [[extracellular matrix]] of [[blood vessel]]s.  It stays [[plasma membrane|membrane]]-bound as long as there is no [[signal peptide]].
Like other FGF family members, basic fibroblast growth factor possess broad [[mitogenic]] and cell survival activities, and is involved in a variety of biological processes, including [[embryonic development]], [[cell growth]], [[morphogenesis]], [[tissue repair]], tumor growth and invasion.
 
In normal tissue, bFGF is present in [[basement membrane]]s and in the [[endothelium|subendothelial]] [[extracellular matrix]] of [[blood vessel]]s.  It stays [[plasma membrane|membrane]]-bound as long as there is no [[signal peptide]].


It has been hypothesized that, during both [[wound healing]] of normal tissues and [[tumor]] development, the action of [[heparan sulfate]]-degrading [[enzyme]]s activates bFGF, thus mediating the formation of new [[blood vessel]]s, a process known as [[angiogenesis]].
It has been hypothesized that, during both [[wound healing]] of normal tissues and [[tumor]] development, the action of [[heparan sulfate]]-degrading [[enzyme]]s activates bFGF, thus mediating the formation of new [[blood vessel]]s, a process known as [[angiogenesis]].


In addition, it is synthesized and secreted by human [[adipocyte]]s and the concentration of bFGF correlates with the BMI in blood samples. In this study, bFGF was also shown to act on [[preosteoblast]]s&nbsp;– in the form of an increased [[cell proliferation|proliferation]]&nbsp;– after binding to [[fibroblast growth factor receptor 1]] and activating [[phosphoinositide 3-kinase]].<ref>{{cite journal | vauthors = Kühn MC, Willenberg HS, Schott M, Papewalis C, Stumpf U, Flohé S, Scherbaum WA, Schinner S | title = Adipocyte-secreted factors increase osteoblast proliferation and the OPG/RANKL ratio to influence osteoclast formation | journal = Molecular and Cellular Endocrinology | volume = 349 | issue = 2 | pages = 180–8 | date = Feb 2012 | pmid = 22040599 | doi = 10.1016/j.mce.2011.10.018 }}</ref>
In addition, it is synthesized and secreted by human [[adipocyte]]s and the concentration of FGF2 correlates with the BMI in blood samples. It was also shown to act on [[preosteoblast]]s&nbsp;– in the form of an increased [[cell proliferation|proliferation]]&nbsp;– after binding to [[fibroblast growth factor receptor 1]] and activating [[phosphoinositide 3-kinase]].<ref>{{cite journal | vauthors = Kühn MC, Willenberg HS, Schott M, Papewalis C, Stumpf U, Flohé S, Scherbaum WA, Schinner S | title = Adipocyte-secreted factors increase osteoblast proliferation and the OPG/RANKL ratio to influence osteoclast formation | journal = Molecular and Cellular Endocrinology | volume = 349 | issue = 2 | pages = 180–8 | date = February 2012 | pmid = 22040599 | doi = 10.1016/j.mce.2011.10.018 }}</ref>


bFGF has been shown in preliminary animal studies to protect the heart from injury associated with a heart attack, reducing tissue death and promoting improved function after [[Reperfusion therapy|reperfusion]].<ref>{{cite journal | vauthors = House SL, Bolte C, Zhou M, Doetschman T, Klevitsky R, Newman G, Schultz Jel J | title = Cardiac-specific overexpression of fibroblast growth factor-2 protects against myocardial dysfunction and infarction in a murine model of low-flow ischemia | journal = Circulation | volume = 108 | issue = 25 | pages = 3140–8 | date = Dec 2003 | pmid = 14656920 | doi = 10.1161/01.CIR.0000105723.91637.1C }}</ref>
FGF2 has been shown in preliminary animal studies to protect the heart from injury associated with a heart attack, reducing tissue death and promoting improved function after [[Reperfusion therapy|reperfusion]].<ref>{{cite journal | vauthors = House SL, Bolte C, Zhou M, Doetschman T, Klevitsky R, Newman G, Schultz Jel J | title = Cardiac-specific overexpression of fibroblast growth factor-2 protects against myocardial dysfunction and infarction in a murine model of low-flow ischemia | journal = Circulation | volume = 108 | issue = 25 | pages = 3140–8 | date = December 2003 | pmid = 14656920 | doi = 10.1161/01.CIR.0000105723.91637.1C }}</ref>


Recent evidence has shown that low levels of FGF2 play a key role in the incidence of excessive anxiety.<ref name="pmid19439615">{{cite journal | vauthors = Perez JA, Clinton SM, Turner CA, Watson SJ, Akil H | title = A new role for FGF2 as an endogenous inhibitor of anxiety | journal = J. Neurosci. | volume = 29 | issue = 19 | pages = 6379–87 | year = 2009 | pmid = 19439615 | pmc = 2748795 | doi = 10.1523/JNEUROSCI.4829-08.2009 }}</ref>
Recent evidence has shown that low levels of FGF2 play a key role in the incidence of excessive anxiety.<ref name="pmid19439615">{{cite journal | vauthors = Perez JA, Clinton SM, Turner CA, Watson SJ, Akil H | title = A new role for FGF2 as an endogenous inhibitor of anxiety | journal = The Journal of Neuroscience | volume = 29 | issue = 19 | pages = 6379–87 | date = May 2009 | pmid = 19439615 | pmc = 2748795 | doi = 10.1523/JNEUROSCI.4829-08.2009 }}</ref>


Additionally, bFGF is a critical component of human [[embryonic stem cell]] culture medium; the growth factor is necessary for the cells to remain in an undifferentiated state, although the mechanisms by which it does this are poorly defined. It has been demonstrated to induce [[Gremlin (protein)|gremlin]] expression which in turn is known to inhibit the induction of differentiation by [[bone morphogenetic proteins]].<ref>{{cite journal | vauthors = Pereira RC, Economides AN, Canalis E | title = Bone morphogenetic proteins induce gremlin, a protein that limits their activity in osteoblasts | journal = Endocrinology | volume = 141 | issue = 12 | pages = 4558–63 | date = Dec 2000 | pmid = 11108268 | doi = 10.1210/en.141.12.4558 | url = http://endo.endojournals.org/cgi/pmidlookup?view=long&pmid=11108268 }}</ref> It is necessary in mouse-feeder cell dependent culture systems, as well as in feeder and serum-free culture systems.<ref>{{cite journal | vauthors = Liu Y, Song Z, Zhao Y, Qin H, Cai J, Zhang H, Yu T, Jiang S, Wang G, Ding M, Deng H | title = A novel chemical-defined medium with bFGF and N2B27 supplements supports undifferentiated growth in human embryonic stem cells | journal = Biochemical and Biophysical Research Communications | volume = 346 | issue = 1 | pages = 131–9 | date = Jul 2006 | pmid = 16753134 | doi = 10.1016/j.bbrc.2006.05.086 }}</ref> FGF2, in conjunction with [[Bone morphogenetic protein 4|BMP4]], promote differentiation of stem cells to mesodermal lineages.  After differentiation, BMP4 and FGF2 treated cells generally produces higher amounts of [[Osteoblast|osteogenic]] and [[Chondrocyte|chondrogenic]] differentiation than untreated stem cells.<ref>{{cite journal | vauthors = Lee TJ, Jang J, Kang S, Jin M, Shin H, Kim DW, Kim BS | title = Enhancement of osteogenic and chondrogenic differentiation of human embryonic stem cells by mesodermal lineage induction with BMP-4 and FGF2 treatment | journal = Biochemical and Biophysical Research Communications | volume = 430 | issue = 2 | pages = 793–7 | date = Jan 2013 | pmid = 23206696 | pmc =  | doi = 10.1016/j.bbrc.2012.11.067 }}</ref>
Additionally, FGF2 is a critical component of human [[embryonic stem cell]] culture medium; the growth factor is necessary for the cells to remain in an undifferentiated state, although the mechanisms by which it does this are poorly defined. It has been demonstrated to induce [[Gremlin (protein)|gremlin]] expression which in turn is known to inhibit the induction of differentiation by [[bone morphogenetic proteins]].<ref>{{cite journal | vauthors = Pereira RC, Economides AN, Canalis E | title = Bone morphogenetic proteins induce gremlin, a protein that limits their activity in osteoblasts | journal = Endocrinology | volume = 141 | issue = 12 | pages = 4558–63 | date = December 2000 | pmid = 11108268 | doi = 10.1210/en.141.12.4558 | url = http://endo.endojournals.org/cgi/pmidlookup?view=long&pmid=11108268 }}</ref> It is necessary in mouse-feeder cell dependent culture systems, as well as in feeder and serum-free culture systems.<ref>{{cite journal | vauthors = Liu Y, Song Z, Zhao Y, Qin H, Cai J, Zhang H, Yu T, Jiang S, Wang G, Ding M, Deng H | title = A novel chemical-defined medium with bFGF and N2B27 supplements supports undifferentiated growth in human embryonic stem cells | journal = Biochemical and Biophysical Research Communications | volume = 346 | issue = 1 | pages = 131–9 | date = July 2006 | pmid = 16753134 | doi = 10.1016/j.bbrc.2006.05.086 }}</ref> FGF2, in conjunction with [[Bone morphogenetic protein 4|BMP4]], promote differentiation of stem cells to mesodermal lineages.  After differentiation, BMP4 and FGF2 treated cells generally produce higher amounts of [[Osteoblast|osteogenic]] and [[Chondrocyte|chondrogenic]] differentiation than untreated stem cells.<ref>{{cite journal | vauthors = Lee TJ, Jang J, Kang S, Jin M, Shin H, Kim DW, Kim BS | title = Enhancement of osteogenic and chondrogenic differentiation of human embryonic stem cells by mesodermal lineage induction with BMP-4 and FGF2 treatment | journal = Biochemical and Biophysical Research Communications | volume = 430 | issue = 2 | pages = 793–7 | date = January 2013 | pmid = 23206696 | pmc =  | doi = 10.1016/j.bbrc.2012.11.067 }}</ref> However, a low concentration of bFGF (10 ng/mL) may exert an inhibitory effect on [[osteoblast]] [[Cellular differentiation|differentiation]].<ref>{{cite journal | vauthors = Del Angel-Mosqueda C, Gutiérrez-Puente Y, López-Lozano AP, Romero-Zavaleta RE, Mendiola-Jiménez A, Medina-De la Garza CE, Márquez-M M, De la Garza-Ramos MA | title = Epidermal growth factor enhances osteogenic differentiation of dental pulp stem cells in vitro | journal = Head & Face Medicine | volume = 11 | pages = 29 | date = September 2015 | pmid = 26334535 | doi = 10.1186/s13005-015-0086-5 }}</ref>


== Interactions ==
== Interactions ==


Basic fibroblast growth factor has been shown to [[Protein-protein interaction|interact]] with [[casein kinase 2, alpha 1]],<ref name=pmid12145206>{{cite journal | vauthors = Skjerpen CS, Nilsen T, Wesche J, Olsnes S | title = Binding of FGF-1 variants to protein kinase CK2 correlates with mitogenicity | journal = The EMBO Journal | volume = 21 | issue = 15 | pages = 4058–69 | date = Aug 2002 | pmid = 12145206 | pmc = 126148 | doi = 10.1093/emboj/cdf402 }}</ref> [[RPL6]]<ref name=pmid9826564>{{cite journal | vauthors = Shen B, Arese M, Gualandris A, Rifkin DB | title = Intracellular association of FGF-2 with the ribosomal protein L6/TAXREB107 | journal = Biochemical and Biophysical Research Communications | volume = 252 | issue = 2 | pages = 524–8 | date = Nov 1998 | pmid = 9826564 | doi = 10.1006/bbrc.1998.9677 }}</ref> and [[ribosomal protein S19]].<ref name=pmid11716516>{{cite journal | vauthors = Soulet F, Al Saati T, Roga S, Amalric F, Bouche G | title = Fibroblast growth factor-2 interacts with free ribosomal protein S19 | journal = Biochemical and Biophysical Research Communications | volume = 289 | issue = 2 | pages = 591–6 | date = Nov 2001 | pmid = 11716516 | doi = 10.1006/bbrc.2001.5960 }}</ref>
Basic fibroblast growth factor has been shown to [[Protein-protein interaction|interact]] with [[casein kinase 2, alpha 1]],<ref name=pmid12145206>{{cite journal | vauthors = Skjerpen CS, Nilsen T, Wesche J, Olsnes S | title = Binding of FGF-1 variants to protein kinase CK2 correlates with mitogenicity | journal = The EMBO Journal | volume = 21 | issue = 15 | pages = 4058–69 | date = August 2002 | pmid = 12145206 | pmc = 126148 | doi = 10.1093/emboj/cdf402 }}</ref> [[RPL6]]<ref name=pmid9826564>{{cite journal | vauthors = Shen B, Arese M, Gualandris A, Rifkin DB | title = Intracellular association of FGF-2 with the ribosomal protein L6/TAXREB107 | journal = Biochemical and Biophysical Research Communications | volume = 252 | issue = 2 | pages = 524–8 | date = November 1998 | pmid = 9826564 | doi = 10.1006/bbrc.1998.9677 }}</ref> and [[ribosomal protein S19]].<ref name=pmid11716516>{{cite journal | vauthors = Soulet F, Al Saati T, Roga S, Amalric F, Bouche G | title = Fibroblast growth factor-2 interacts with free ribosomal protein S19 | journal = Biochemical and Biophysical Research Communications | volume = 289 | issue = 2 | pages = 591–6 | date = November 2001 | pmid = 11716516 | doi = 10.1006/bbrc.2001.5960 }}</ref>


== See also ==
== See also ==
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{{Refbegin|33em}}
{{Refbegin|33em}}
* {{cite journal | vauthors = Ornitz DM, Itoh N | title = Fibroblast growth factors | journal = Genome Biology | volume = 2 | issue = 3 | pages = REVIEWS3005 | year = 2001 | pmid = 11276432 | pmc = 138918 | doi = 10.1186/gb-2001-2-3-reviews3005 }}
* {{cite journal | vauthors = Ornitz DM, Itoh N | title = Fibroblast growth factors | journal = Genome Biology | volume = 2 | issue = 3 | pages = REVIEWS3005 | year = 2001 | pmid = 11276432 | pmc = 138918 | doi = 10.1186/gb-2001-2-3-reviews3005 }}
* {{cite journal | vauthors = Orpana A, Salven P | title = Angiogenic and lymphangiogenic molecules in hematological malignancies | journal = Leukemia & Lymphoma | volume = 43 | issue = 2 | pages = 219–24 | date = Feb 2002 | pmid = 11999550 | doi = 10.1080/10428190290005964 }}
* {{cite journal | vauthors = Orpana A, Salven P | title = Angiogenic and lymphangiogenic molecules in hematological malignancies | journal = Leukemia & Lymphoma | volume = 43 | issue = 2 | pages = 219–24 | date = February 2002 | pmid = 11999550 | doi = 10.1080/10428190290005964 }}
* {{cite journal | vauthors = Marie PJ, Debiais F, Haÿ E | title = Regulation of human cranial osteoblast phenotype by FGF-2, FGFR-2 and BMP-2 signaling | journal = Histology and Histopathology | volume = 17 | issue = 3 | pages = 877–85 | year = 2003 | pmid = 12168799 | doi = }}
* {{cite journal | vauthors = Marie PJ, Debiais F, Haÿ E | title = Regulation of human cranial osteoblast phenotype by FGF-2, FGFR-2 and BMP-2 signaling | journal = Histology and Histopathology | volume = 17 | issue = 3 | pages = 877–85 | year = 2003 | pmid = 12168799 | doi = 10.14670/HH-17.877 }}
* {{cite journal | vauthors = Zhao XC, Zhang LM, Tong DY, An P, Jiang C, Zhao P, Chen WM, Wang J | title = Propofol increases expression of basic fibroblast growth factor after transient cerebral ischemia in rats | journal = Neurochemical Research | volume = 38 | issue = 3 | pages = 530–7 | date = Mar 2013 | pmid = 23247820 | pmc = 3574197 | doi = 10.1007/s11064-012-0945-4 }}
* {{cite journal | vauthors = Zhao XC, Zhang LM, Tong DY, An P, Jiang C, Zhao P, Chen WM, Wang J | title = Propofol increases expression of basic fibroblast growth factor after transient cerebral ischemia in rats | journal = Neurochemical Research | volume = 38 | issue = 3 | pages = 530–7 | date = March 2013 | pmid = 23247820 | pmc = 3574197 | doi = 10.1007/s11064-012-0945-4 }}
* {{cite journal | vauthors = Vincent T, Saklatvala J | title = Basic fibroblast growth factor: an extracellular mechanotransducer in articular cartilage? | journal = Biochemical Society Transactions | volume = 34 | issue = Pt 3 | pages = 456–7 | date = Jun 2006 | pmid = 16709186 | doi = 10.1042/BST0340456 }}
* {{cite journal | vauthors = Vincent T, Saklatvala J | title = Basic fibroblast growth factor: an extracellular mechanotransducer in articular cartilage? | journal = Biochemical Society Transactions | volume = 34 | issue = Pt 3 | pages = 456–7 | date = June 2006 | pmid = 16709186 | doi = 10.1042/BST0340456 }}
* {{cite journal | vauthors = Ribatti D, Vacca A, Rusnati M, Presta M | title = The discovery of basic fibroblast growth factor/fibroblast growth factor-2 and its role in haematological malignancies | journal = Cytokine & Growth Factor Reviews | volume = 18 | issue = 3-4 | pages = 327–34 | year = 2007 | pmid = 17537668 | doi = 10.1016/j.cytogfr.2007.04.011 }}
* {{cite journal | vauthors = Ribatti D, Vacca A, Rusnati M, Presta M | title = The discovery of basic fibroblast growth factor/fibroblast growth factor-2 and its role in haematological malignancies | journal = Cytokine & Growth Factor Reviews | volume = 18 | issue = 3-4 | pages = 327–34 | year = 2007 | pmid = 17537668 | doi = 10.1016/j.cytogfr.2007.04.011 }}
* {{cite journal | vauthors = Watson R, Anthony F, Pickett M, Lambden P, Masson GM, Thomas EJ | title = Reverse transcription with nested polymerase chain reaction shows expression of basic fibroblast growth factor transcripts in human granulosa and cumulus cells from in vitro fertilisation patients | journal = Biochemical and Biophysical Research Communications | volume = 187 | issue = 3 | pages = 1227–31 | date = Sep 1992 | pmid = 1417798 | doi = 10.1016/0006-291X(92)90434-M }}
* {{cite journal | vauthors = Watson R, Anthony F, Pickett M, Lambden P, Masson GM, Thomas EJ | title = Reverse transcription with nested polymerase chain reaction shows expression of basic fibroblast growth factor transcripts in human granulosa and cumulus cells from in vitro fertilisation patients | journal = Biochemical and Biophysical Research Communications | volume = 187 | issue = 3 | pages = 1227–31 | date = September 1992 | pmid = 1417798 | doi = 10.1016/0006-291X(92)90434-M }}
* {{cite journal | vauthors = Zhu X, Komiya H, Chirino A, Faham S, Fox GM, Arakawa T, Hsu BT, Rees DC | title = Three-dimensional structures of acidic and basic fibroblast growth factors | journal = Science | volume = 251 | issue = 4989 | pages = 90–3 | date = Jan 1991 | pmid = 1702556 | doi = 10.1126/science.1702556 }}
* {{cite journal | vauthors = Zhu X, Komiya H, Chirino A, Faham S, Fox GM, Arakawa T, Hsu BT, Rees DC | title = Three-dimensional structures of acidic and basic fibroblast growth factors | journal = Science | volume = 251 | issue = 4989 | pages = 90–3 | date = January 1991 | pmid = 1702556 | doi = 10.1126/science.1702556 }}
* {{cite journal | vauthors = Eriksson AE, Cousens LS, Weaver LH, Matthews BW | title = Three-dimensional structure of human basic fibroblast growth factor | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 88 | issue = 8 | pages = 3441–5 | date = Apr 1991 | pmid = 1707542 | pmc = 51463 | doi = 10.1073/pnas.88.8.3441 }}
* {{cite journal | vauthors = Eriksson AE, Cousens LS, Weaver LH, Matthews BW | title = Three-dimensional structure of human basic fibroblast growth factor | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 88 | issue = 8 | pages = 3441–5 | date = April 1991 | pmid = 1707542 | pmc = 51463 | doi = 10.1073/pnas.88.8.3441 }}
* {{cite journal | vauthors = Ago H, Kitagawa Y, Fujishima A, Matsuura Y, Katsube Y | title = Crystal structure of basic fibroblast growth factor at 1.6 A resolution | journal = Journal of Biochemistry | volume = 110 | issue = 3 | pages = 360–3 | date = Sep 1991 | pmid = 1769963 | doi =  }}
* {{cite journal | vauthors = Ago H, Kitagawa Y, Fujishima A, Matsuura Y, Katsube Y | title = Crystal structure of basic fibroblast growth factor at 1.6 A resolution | journal = Journal of Biochemistry | volume = 110 | issue = 3 | pages = 360–3 | date = September 1991 | pmid = 1769963 | doi =  }}
* {{cite journal | vauthors = Florkiewicz RZ, Shibata F, Barankiewicz T, Baird A, Gonzalez AM, Florkiewicz E, Shah N | title = Basic fibroblast growth factor gene expression | journal = Annals of the New York Academy of Sciences | volume = 638 | issue =  | pages = 109–26 | year = 1992 | pmid = 1785797 | doi = 10.1111/j.1749-6632.1991.tb49022.x }}
* {{cite journal | vauthors = Zhang JD, Cousens LS, Barr PJ, Sprang SR | title = Three-dimensional structure of human basic fibroblast growth factor, a structural homolog of interleukin 1 beta | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 88 | issue = 8 | pages = 3446–50 | date = April 1991 | pmid = 1849658 | pmc = 51464 | doi = 10.1073/pnas.88.8.3446 }}
* {{cite journal | vauthors = Zhang JD, Cousens LS, Barr PJ, Sprang SR | title = Three-dimensional structure of human basic fibroblast growth factor, a structural homolog of interleukin 1 beta | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 88 | issue = 8 | pages = 3446–50 | date = Apr 1991 | pmid = 1849658 | pmc = 51464 | doi = 10.1073/pnas.88.8.3446 }}
* {{cite journal | vauthors = Wu DQ, Kan MK, Sato GH, Okamoto T, Sato JD | title = Characterization and molecular cloning of a putative binding protein for heparin-binding growth factors | journal = The Journal of Biological Chemistry | volume = 266 | issue = 25 | pages = 16778–85 | date = September 1991 | pmid = 1885605 | doi =  }}
* {{cite journal | vauthors = Wu DQ, Kan MK, Sato GH, Okamoto T, Sato JD | title = Characterization and molecular cloning of a putative binding protein for heparin-binding growth factors | journal = The Journal of Biological Chemistry | volume = 266 | issue = 25 | pages = 16778–85 | date = Sep 1991 | pmid = 1885605 | doi =  }}
* {{cite journal | vauthors = Fukushima Y, Byers MG, Fiddes JC, Shows TB | title = The human basic fibroblast growth factor gene (FGFB) is assigned to chromosome 4q25 | journal = Cytogenetics and Cell Genetics | volume = 54 | issue = 3-4 | pages = 159–60 | year = 1991 | pmid = 2265560 | doi = 10.1159/000132983 }}
* {{cite journal | vauthors = Fukushima Y, Byers MG, Fiddes JC, Shows TB | title = The human basic fibroblast growth factor gene (FGFB) is assigned to chromosome 4q25 | journal = Cytogenetics and Cell Genetics | volume = 54 | issue = 3-4 | pages = 159–60 | year = 1991 | pmid = 2265560 | doi = 10.1159/000132983 }}
* {{cite journal | vauthors = Lafage-Pochitaloff M, Galland F, Simonetti J, Prats H, Mattei MG, Birnbaum D | title = The human basic fibroblast growth factor gene is located on the long arm of chromosome 4 at bands q26-q27 | journal = Oncogene Research | volume = 5 | issue = 3 | pages = 241–4 | year = 1990 | pmid = 2320377 | doi =  }}
* {{cite journal | vauthors = Lafage-Pochitaloff M, Galland F, Simonetti J, Prats H, Mattei MG, Birnbaum D | title = The human basic fibroblast growth factor gene is located on the long arm of chromosome 4 at bands q26-q27 | journal = Oncogene Research | volume = 5 | issue = 3 | pages = 241–4 | year = 1990 | pmid = 2320377 | doi =  }}
* {{cite journal | vauthors = Story MT, Esch F, Shimasaki S, Sasse J, Jacobs SC, Lawson RK | title = Amino-terminal sequence of a large form of basic fibroblast growth factor isolated from human benign prostatic hyperplastic tissue | journal = Biochemical and Biophysical Research Communications | volume = 142 | issue = 3 | pages = 702–9 | date = Feb 1987 | pmid = 2435284 | doi = 10.1016/0006-291X(87)91471-9 }}
* {{cite journal | vauthors = Story MT, Esch F, Shimasaki S, Sasse J, Jacobs SC, Lawson RK | title = Amino-terminal sequence of a large form of basic fibroblast growth factor isolated from human benign prostatic hyperplastic tissue | journal = Biochemical and Biophysical Research Communications | volume = 142 | issue = 3 | pages = 702–9 | date = February 1987 | pmid = 2435284 | doi = 10.1016/0006-291X(87)91471-9 }}
* {{cite journal | vauthors = Kurokawa T, Sasada R, Iwane M, Igarashi K | title = Cloning and expression of cDNA encoding human basic fibroblast growth factor | journal = FEBS Letters | volume = 213 | issue = 1 | pages = 189–94 | date = Mar 1987 | pmid = 2435575 | doi = 10.1016/0014-5793(87)81489-8 }}
* {{cite journal | vauthors = Kurokawa T, Sasada R, Iwane M, Igarashi K | title = Cloning and expression of cDNA encoding human basic fibroblast growth factor | journal = FEBS Letters | volume = 213 | issue = 1 | pages = 189–94 | date = March 1987 | pmid = 2435575 | doi = 10.1016/0014-5793(87)81489-8 }}
* {{cite journal | vauthors = Prats H, Kaghad M, Prats AC, Klagsbrun M, Lélias JM, Liauzun P, Chalon P, Tauber JP, Amalric F, Smith JA | title = High molecular mass forms of basic fibroblast growth factor are initiated by alternative CUG codons | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 86 | issue = 6 | pages = 1836–40 | date = Mar 1989 | pmid = 2538817 | pmc = 286799 | doi = 10.1073/pnas.86.6.1836 }}
* {{cite journal | vauthors = Prats H, Kaghad M, Prats AC, Klagsbrun M, Lélias JM, Liauzun P, Chalon P, Tauber JP, Amalric F, Smith JA | title = High molecular mass forms of basic fibroblast growth factor are initiated by alternative CUG codons | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 86 | issue = 6 | pages = 1836–40 | date = March 1989 | pmid = 2538817 | pmc = 286799 | doi = 10.1073/pnas.86.6.1836 }}
* {{cite journal | vauthors = Florkiewicz RZ, Sommer A | title = Human basic fibroblast growth factor gene encodes four polypeptides: three initiate translation from non-AUG codons | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 86 | issue = 11 | pages = 3978–81 | date = Jun 1989 | pmid = 2726761 | pmc = 287371 | doi = 10.1073/pnas.86.11.3978 }}
* {{cite journal | vauthors = Florkiewicz RZ, Sommer A | title = Human basic fibroblast growth factor gene encodes four polypeptides: three initiate translation from non-AUG codons | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 86 | issue = 11 | pages = 3978–81 | date = June 1989 | pmid = 2726761 | pmc = 287371 | doi = 10.1073/pnas.86.11.3978 }}
* {{cite journal | vauthors = Abraham JA, Whang JL, Tumolo A, Mergia A, Fiddes JC | title = Human basic fibroblast growth factor: nucleotide sequence, genomic organization, and expression in mammalian cells | journal = Cold Spring Harbor Symposia on Quantitative Biology | volume = 51 Pt 1 | issue =  | pages = 657–68 | year = 1987 | pmid = 3472745 | doi = 10.1101/sqb.1986.051.01.078 }}
* {{cite journal | vauthors = Abraham JA, Whang JL, Tumolo A, Mergia A, Fiddes JC | title = Human basic fibroblast growth factor: nucleotide sequence, genomic organization, and expression in mammalian cells | journal = Cold Spring Harbor Symposia on Quantitative Biology | volume = 51 Pt 1 | issue =  | pages = 657–68 | year = 1987 | pmid = 3472745 | doi = 10.1101/sqb.1986.051.01.078 }}
* {{cite journal | vauthors = Sommer A, Brewer MT, Thompson RC, Moscatelli D, Presta M, Rifkin DB | title = A form of human basic fibroblast growth factor with an extended amino terminus | journal = Biochemical and Biophysical Research Communications | volume = 144 | issue = 2 | pages = 543–50 | date = Apr 1987 | pmid = 3579930 | doi = 10.1016/S0006-291X(87)80001-3 }}
* {{cite journal | vauthors = Sommer A, Brewer MT, Thompson RC, Moscatelli D, Presta M, Rifkin DB | title = A form of human basic fibroblast growth factor with an extended amino terminus | journal = Biochemical and Biophysical Research Communications | volume = 144 | issue = 2 | pages = 543–50 | date = April 1987 | pmid = 3579930 | doi = 10.1016/S0006-291X(87)80001-3 }}
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[[Category:Growth factors]]
[[Category:Growth factors]]


[[de:Wachstumsfaktor]]
[[de:Wachstumsfaktor]]
[[es:Factor de crecimiento]]
[[es:Factor de crecimiento]]

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FGF2, also known as basic fibroblast growth factor (bFGF) and FGF-β, is a growth factor and signaling protein encoded by the FGF2 gene.[1][2] It is synthesized primarily as a 155 amino acid polypeptide, resulting in an 18 kDa protein. However, there are four alternate start codons which provide N-terminal extensions of 41, 46, 55, or 133 amino acids, resulting in proteins of 22 kDa (196 aa total), 22.5 kDa (201 aa total), 24 kDa (210 aa total) and 34 kDa (288 aa total), respectively.[3] Generally, the 155 aa/18 kDa low molecular weight (LMW) form is considered cytoplasmic and can be secreted from the cell, whereas the high molecular weight (HMW) forms are directed to the cell's nucleus.[4]

Fibroblast growth factor protein was first purified in 1975, but soon afterwards others using different conditions isolated basic FGF, Heparin-binding growth factor-2, and Endothelial cell growth factor-2. Gene sequencing revealed that this group was in fact the same FGF2 protein and that it was a member of a family of FGF proteins.[3][5] FGF2 binds to and exerts effects via specific fibroblast growth factor receptor (FGFR) proteins which themselves constitute a family of closely related molecules.

Function

Like other FGF family members, basic fibroblast growth factor possess broad mitogenic and cell survival activities, and is involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion.

In normal tissue, bFGF is present in basement membranes and in the subendothelial extracellular matrix of blood vessels. It stays membrane-bound as long as there is no signal peptide.

It has been hypothesized that, during both wound healing of normal tissues and tumor development, the action of heparan sulfate-degrading enzymes activates bFGF, thus mediating the formation of new blood vessels, a process known as angiogenesis.

In addition, it is synthesized and secreted by human adipocytes and the concentration of FGF2 correlates with the BMI in blood samples. It was also shown to act on preosteoblasts – in the form of an increased proliferation – after binding to fibroblast growth factor receptor 1 and activating phosphoinositide 3-kinase.[6]

FGF2 has been shown in preliminary animal studies to protect the heart from injury associated with a heart attack, reducing tissue death and promoting improved function after reperfusion.[7]

Recent evidence has shown that low levels of FGF2 play a key role in the incidence of excessive anxiety.[8]

Additionally, FGF2 is a critical component of human embryonic stem cell culture medium; the growth factor is necessary for the cells to remain in an undifferentiated state, although the mechanisms by which it does this are poorly defined. It has been demonstrated to induce gremlin expression which in turn is known to inhibit the induction of differentiation by bone morphogenetic proteins.[9] It is necessary in mouse-feeder cell dependent culture systems, as well as in feeder and serum-free culture systems.[10] FGF2, in conjunction with BMP4, promote differentiation of stem cells to mesodermal lineages. After differentiation, BMP4 and FGF2 treated cells generally produce higher amounts of osteogenic and chondrogenic differentiation than untreated stem cells.[11] However, a low concentration of bFGF (10 ng/mL) may exert an inhibitory effect on osteoblast differentiation.[12]

Interactions

Basic fibroblast growth factor has been shown to interact with casein kinase 2, alpha 1,[13] RPL6[14] and ribosomal protein S19.[15]

See also

References

  1. ↑ Dionne CA, Crumley G, Bellot F, Kaplow JM, Searfoss G, Ruta M, Burgess WH, Jaye M, Schlessinger J (September 1990). "Cloning and expression of two distinct high-affinity receptors cross-reacting with acidic and basic fibroblast growth factors". The EMBO Journal. 9 (9): 2685–92. PMC 551973. PMID 1697263.
  2. ↑ Kim HS (1998). "Assignment1 of the human basic fibroblast growth factor gene FGF2 to chromosome 4 band q26 by radiation hybrid mapping". Cytogenetics and Cell Genetics. 83 (1–2): 73. doi:10.1159/000015129. PMID 9925931.
  3. ↑ 3.0 3.1 Florkiewicz RZ, Shibata F, Barankiewicz T, Baird A, Gonzalez AM, Florkiewicz E, Shah N (December 1991). "Basic fibroblast growth factor gene expression". Annals of the New York Academy of Sciences. 638 (1): 109–26. doi:10.1111/j.1749-6632.1991.tb49022.x. PMID 1785797.
  4. ↑ Coleman SJ, Bruce C, Chioni AM, Kocher HM, Grose RP (August 2014). "The ins and outs of fibroblast growth factor receptor signalling". Clinical Science. 127 (4): 217–31. doi:10.1042/CS20140100. PMID 24780002.
  5. ↑ Burgess WH, Maciag T (1989). "The heparin-binding (fibroblast) growth factor family of proteins". Annual Review of Biochemistry. 58: 575–606. doi:10.1146/annurev.bi.58.070189.003043. PMID 2549857.
  6. ↑ Kühn MC, Willenberg HS, Schott M, Papewalis C, Stumpf U, Flohé S, Scherbaum WA, Schinner S (February 2012). "Adipocyte-secreted factors increase osteoblast proliferation and the OPG/RANKL ratio to influence osteoclast formation". Molecular and Cellular Endocrinology. 349 (2): 180–8. doi:10.1016/j.mce.2011.10.018. PMID 22040599.
  7. ↑ House SL, Bolte C, Zhou M, Doetschman T, Klevitsky R, Newman G, Schultz Jel J (December 2003). "Cardiac-specific overexpression of fibroblast growth factor-2 protects against myocardial dysfunction and infarction in a murine model of low-flow ischemia". Circulation. 108 (25): 3140–8. doi:10.1161/01.CIR.0000105723.91637.1C. PMID 14656920.
  8. ↑ Perez JA, Clinton SM, Turner CA, Watson SJ, Akil H (May 2009). "A new role for FGF2 as an endogenous inhibitor of anxiety". The Journal of Neuroscience. 29 (19): 6379–87. doi:10.1523/JNEUROSCI.4829-08.2009. PMC 2748795. PMID 19439615.
  9. ↑ Pereira RC, Economides AN, Canalis E (December 2000). "Bone morphogenetic proteins induce gremlin, a protein that limits their activity in osteoblasts". Endocrinology. 141 (12): 4558–63. doi:10.1210/en.141.12.4558. PMID 11108268.
  10. ↑ Liu Y, Song Z, Zhao Y, Qin H, Cai J, Zhang H, Yu T, Jiang S, Wang G, Ding M, Deng H (July 2006). "A novel chemical-defined medium with bFGF and N2B27 supplements supports undifferentiated growth in human embryonic stem cells". Biochemical and Biophysical Research Communications. 346 (1): 131–9. doi:10.1016/j.bbrc.2006.05.086. PMID 16753134.
  11. ↑ Lee TJ, Jang J, Kang S, Jin M, Shin H, Kim DW, Kim BS (January 2013). "Enhancement of osteogenic and chondrogenic differentiation of human embryonic stem cells by mesodermal lineage induction with BMP-4 and FGF2 treatment". Biochemical and Biophysical Research Communications. 430 (2): 793–7. doi:10.1016/j.bbrc.2012.11.067. PMID 23206696.
  12. ↑ Del Angel-Mosqueda C, Gutiérrez-Puente Y, López-Lozano AP, Romero-Zavaleta RE, Mendiola-Jiménez A, Medina-De la Garza CE, Márquez-M M, De la Garza-Ramos MA (September 2015). "Epidermal growth factor enhances osteogenic differentiation of dental pulp stem cells in vitro". Head & Face Medicine. 11: 29. doi:10.1186/s13005-015-0086-5. PMID 26334535.
  13. ↑ Skjerpen CS, Nilsen T, Wesche J, Olsnes S (August 2002). "Binding of FGF-1 variants to protein kinase CK2 correlates with mitogenicity". The EMBO Journal. 21 (15): 4058–69. doi:10.1093/emboj/cdf402. PMC 126148. PMID 12145206.
  14. ↑ Shen B, Arese M, Gualandris A, Rifkin DB (November 1998). "Intracellular association of FGF-2 with the ribosomal protein L6/TAXREB107". Biochemical and Biophysical Research Communications. 252 (2): 524–8. doi:10.1006/bbrc.1998.9677. PMID 9826564.
  15. ↑ Soulet F, Al Saati T, Roga S, Amalric F, Bouche G (November 2001). "Fibroblast growth factor-2 interacts with free ribosomal protein S19". Biochemical and Biophysical Research Communications. 289 (2): 591–6. doi:10.1006/bbrc.2001.5960. PMID 11716516.

Further reading

External links

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