Conserved Site

Platelet-derived growth factor, conserved site (IPR023581)

Short name: PD_growth_factor_CS


Platelet-derived growth factor (PDGF) [PMID: 2546599, PMID: 1425569,PMID: 7640655] is a potent mitogen for cells of mesenchymal origin, including smooth muscle cells and glial cells. In both mouse and human, the PDGF signalling network consists of four ligands, PDGFA-D, and two receptors, PDGFRalpha and PDGFRbeta. All PDGFs function as secreted, disulphide-linked homodimers, but only PDGFA and B can form functional heterodimers. PDGFRs also function as homo- and heterodimers. All known PDGFs have characteristic 'PDGF domains', which include eight conserved cysteines that are involved in inter- and intramolecular bonds. 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 Woolly monkey sarcoma virus (WMSV) (Simian sarcoma virus), encoded by the v-sis oncogene, is derived from the B chain of PDGF.

PDGFs are mitogenic during early developmental stages, driving the proliferation of undifferentiated mesenchyme and some progenitor populations. During later maturation stages, PDGF signalling has been implicated in tissue remodelling and cellular differentiation, and in inductive events involved in patterning and morphogenesis. In addition to driving mesenchymal proliferation, PDGFs have been shown to direct the migration, differentiation and function of a variety of specialised mesenchymal and migratory cell types, both during development and in the adult animal [PMID: 12952899].

Other growth factors in this family include vascular endothelial growth factors B and C (VEGF-B, VEGF-C) [PMID: 8637916, PMID: 8617204] which are active in angiogenesis and endothelial cell growth, and placenta growth factor (PlGF) which is also active in angiogenesis [PMID: 7681160]. VEGF is a potent mitogen in embryonic and somatic angiogenesis with a unique specificity for vascular endothelial cells. VEGF forms homodimers and exists in 4 different isoforms. Overall, the VEGF monomer resembles that of PDGF, but its N-terminal segment is helical rather than extended.

PDGF is structurally related to a number of other growth factors which also form disulphide-linked homo- or heterodimers. A cysteine knot motif is a common feature of this domain [PMID: 8323751,PMID: 9207067,PMID: 11345501].

This entry represents a conserved site found in PDGF and VEGF families, amongst others, that includes 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 disulphide bonds [PMID: 1396586].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE patterns