PI3K reg class IA, PDGF-A, PDGF-R-beta, Tyk2, SOS, PDGF receptor, IKK-alpha, c-Src, GRB2, PI3K cat class IA, PtdIns(3,4,5)P3, JAK2, 184.108.40.206, IKK (cat), STAT6, c-Myc, NF-kB, STAT1, I-kB, STAT3, Shc, STAT5, RelA (p65 NF-kB subunit), JAK1, PDGF-R-alpha, PKR, H-Ras, AKT(PKB), NF-kB p65/p65, PDGF-B, c-Fos, PtdIns(4,5)P2
PDGF-induced anti-apoptosis and proliferation of cells via STAT and NF-KB pathways
Platelet-derived growth factors ( PDGF s) are members of a large family of growth factors secreted by human vascular endothelial cells and fibroblasts.
The PDGF family is composed of four different polypeptide chains encoded by four different genes. There are two classical PDGF chains, PDGF-A and PDGF-B, and two only recently discovered chains, PDGF-C and PDGF-D. The four PDGF chains assemble into disulphide-bonded dimers via homo- or heterodimerization.
PDGF s regulate biological functions in cells through binding to specific structurally related high-affinity receptors ( PDGFR ) on cell surface, denoted PDGFR alpha and beta. Upon ligand binding, the PDGFR dimerizes and autophosphorylates on a number of tyrosine residues. Tyrosine phosphorylated sites are used by PDGFR as anchor sites for various SH2 domain-containing proteins .
PDGF is a principal survival factor that inhibits apoptosis and promotes proliferation. The mechanisms of cellular proliferation and transformation are intrinsically linked to the process of apoptosis: the default of proliferating cells is to undergo apoptosis unless specific survival signals are provided .
It is show, that PDGF-B ,  and sometimes PDGF-A  regulate of cell growth and survival via the Signal transducer and activator of transcription ( STAT ) pathway  and/or of through Nuclear factors of kappa light polypeptide in B-cells ( NF-KB) . PDGFR -beta and, to a lesser degree, PDGFR -alpha participate in these processes .
Activated PDGFR s directly ,  or indirectly (via activate members of the Janus kinase family (JAK) including JAK1/JAK2 and/or Tyrosine kinase 2 ( TYK2 ) , , . JAK1/JAK2 or TYK2 signaling then lead to the stimulation of members of the STAT family ( STAT1, STAT3, STAT5, STAT6 ). However, STAT3 may also be stimulated by the proto-oncogene tyrosine-protein kinase ( c-Src ) and the Double-stranded RNA-activated protein kinase ( PKR ). PKR is pre-associated with STAT3 and PDGFR -beta. It may facilitate tyrosine phosphorylation of STAT3 by c-Src .
Upon PDGF stimulation, PDGFRs activate Phosphatidylinositol 3-kinase ( PI3K ) directly or indirectly (via Src homology 2 domain containing transforming protein ( Shc )/ Factor receptor bound 2 ( Grb2 ). The PI3K regulatory subunit ( PI3K reg 1A ) stimulates activity of PI3K catalytic subunits ( PI3K cat 1A ), which in turn catalyzes of reaction conversion Phosphatidylinositol-4,5-biphosphate ( PtdIns(4,5)P2 ) into Phosphatidylinositol-3,4,5-trisphosphate ( PtdIns(3,4,5)P3 ). PtdIns(3,4,5)P3 binds to the pleckstrin-homology domain of serine/threonine protein kinase Akt, to recruit Akt to the plasma membrane. When Akt transiently associates with Inhibitor of nuclear factor kappa B kinase catalytic subunits ( IKK ), it phosphorilates and activates IKK. IKK phosphorylates and markes for degradation of NF-KB inhibitor ( I-KB ), thereby inducing NF-kB DNA-binding activity.
However, under certain circumstances, Akt can activate NF-KB through a mechanism that does not involve I-KB degradation by modulating the transcriptional potential of transcription factor p65 ( RelA ). RelA is a component of NF-KB complex .
NF-KB regulates transcription of c-Myc. c-Myc is a central regulator of cell growth, death and differentiation. c-Myc is required for cell proliferation but, in the absence of survival factors, it induces apoptosis. Thus, PDGF stimulates c-Myc -mediated proliferation by activating the H-Ras/ PI3K/ Akt pathway .