{PDOC00222} {PS00249; PDGF_1} {PS50278; PDGF_2} {BEGIN} ********************************************************************** * Platelet-derived growth factor (PDGF) family signature and profile * ********************************************************************** Platelet-derived growth factor (PDGF) [1,2] is a potent mitogen for cells of mesenchymal origin, including smooth muscle cells and glial cells. PDGF consists of two different but closely related chains (A and B chains) which assemble to form disulfide linked homo- or heterodimers (A-A, B-B, an A-B). Alternate splicing of the A chain transcript can give rise to two different forms that differ only in their C-terminal extremity. The transforming protein of simian sarcoma virus (SSV), encoded by the v-sis oncogene, is derived from the B chain of PDGF. PDGF is structurally related to a number of other growth factors which also form disulfide-linked homo- or heterodimers: - Vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF) [3], a growth factor active in angiogenesis and endothelial cell growth. The genome of the orf poxvirus encodes an homolog of VEGF [4]. - Vascular endothelial growth factor B (VEGF-B), also active in angiogenesis and endothelial cell growth [5]. - Vascular endothelial growth factor B (VEGF-C), also active in angiogenesis and endothelial cell growth [6]. - Placenta growth factor (PlGF) [7], which is also active in agiogenesis. As a signature pattern for this family of growth factors, we selected a region that include four of the eight cysteines conserved in the sequences of these proteins. In PDGF, these cysteines are known to be involved in intra- and inter-chain disulfide bonds [8]. We also developed a profile that spans the eight conserved cysteines. -Consensus pattern: P-[PSR]-C-V-x(3)-R-C-[GSTA]-G-C-C [The 4 C's are involved in disulfide bonds] -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: December 2004 / Pattern and text revised. [ 1] Hannink M., Donoghue D.J. "Structure and function of platelet-derived growth factor (PDGF) and related proteins." Biochim. Biophys. Acta 989:1-10(1989). PubMed=2546599 [ 2] Heldin C.-H. "Structural and functional studies on platelet-derived growth factor." EMBO J. 11:4251-4259(1992). PubMed=1425569 [ 3] Ferrara N., Houck K.A., Jakeman L.B., Winer J., Leung D.W. "The vascular endothelial growth factor family of polypeptides." J. Cell. Biochem. 47:211-218(1991). PubMed=1791185 [ 4] Lyttle D.J., Fraser K.M., Fleming S.B., Mercer A.A., Robinson A.J. "Homologs of vascular endothelial growth factor are encoded by the poxvirus orf virus." J. Virol. 68:84-92(1994). PubMed=8254780 [ 5] Olofsson B., Pajusola K., Kaipainen A., von Euler G., Joukov V., Saksela O., Orpana A., Pettersson R.F., Alitalo K., Eriksson U. Proc. Natl. Acad. Sci. U.S.A. 93:2567-2581(1996). [ 6] Joukov V., Pajusola K., Kaipainen A., Chilov D., Lahtinen I., Kukk E., Saksela O., Kalkkinen N., Alitalo K. "A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases." EMBO J. 15:290-298(1996). PubMed=8617204 [ 7] Maglione D., Guerriero V., Viglietto G., Ferraro M.G., Aprelikova O., Alitalo K., Del Vecchio S., Lei K.J., Chou J.Y., Persico M.G. "Two alternative mRNAs coding for the angiogenic factor, placenta growth factor (PlGF), are transcribed from a single gene of chromosome 14." Oncogene 8:925-931(1993). PubMed=7681160 [ 8] Oefner C., D'Arcy A., Winkler F.K., Eggimann B., Hosang M. "Crystal structure of human platelet-derived growth factor BB." EMBO J. 11:3921-3926(1992). PubMed=1396586 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}