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PDGFR
Members of the platelet-derived growth factor (PDGF) family stimulate the proliferation, survival and migration of mesenchymal cells and other cell types. The family consists of five isoforms, i.e. homodimers of A-, B-, C- and D-polypeptide chains and the AB-heterodimer, whichhave important functions during the embryonal development and in the control of tissue homeostasis in the adult. The PDGF isoforms act on their target cells via binding to structurally similar- and-tyrosine kinase receptors (PDGFR and PDGFR, respectively). Over-activity of PDGF signaling has been associated with the development of malignancies and other diseases involving excess cell proliferation. During embryonal development, PDGF isoforms are produced by epithelial and endothelial cells and act in a paracrine manner on neighboring mesenchymal cells, such as fibroblasts, pericytes and smooth muscle cells. There are a few tumor types in which mutations in the genes for PDGF isoforms or receptors drive tumor development.
Certain signaling molecules contain enzymatic activities, such as phospholipase C-(PLC), tyrosine kinases of the Src and Fer families, the GTP:ase activating protein (GAP) for Ras, and the SHP -2 tyrosine phosphatase. The autophosphorylated PDGF receptors also bind members of the STAT family which after phosphorylation by the receptors are activated and translocated into the nucleus, where they act as transcription factors. Other PDGF receptor binding molecules are adapt or molecules which form bridges to other signaling molecules; examples include the p85 regulatory subunit of phosphatidylinositol 3´-kinase (PI3-kinase) forming a complex with the p110 catalytic subunit, Grb2 forming a complex with the nucleotide exchange factor Sos1 which activates Ras and the downstream Erk1/2 MAPK-kinase pathway, as well as other adaptor molecules, including Nck, Shc,Crk and GAB2, which mediate interactions with many downstream signaling pathways. PDGF stimulation indirectly activates a number of additional signaling pathways, such as JNK, p38 and Erk5 MAP-kinase pathways and the small GTP:ases Rac, Rho and Cdc42. All these signaling pathways lead to stimulation of cell proliferation, survival and migration.
References
1.Heldin CH,et al. J Intern Med. 2018;283(1):16–44.
Certain signaling molecules contain enzymatic activities, such as phospholipase C-(PLC), tyrosine kinases of the Src and Fer families, the GTP:ase activating protein (GAP) for Ras, and the SHP -2 tyrosine phosphatase. The autophosphorylated PDGF receptors also bind members of the STAT family which after phosphorylation by the receptors are activated and translocated into the nucleus, where they act as transcription factors. Other PDGF receptor binding molecules are adapt or molecules which form bridges to other signaling molecules; examples include the p85 regulatory subunit of phosphatidylinositol 3´-kinase (PI3-kinase) forming a complex with the p110 catalytic subunit, Grb2 forming a complex with the nucleotide exchange factor Sos1 which activates Ras and the downstream Erk1/2 MAPK-kinase pathway, as well as other adaptor molecules, including Nck, Shc,Crk and GAB2, which mediate interactions with many downstream signaling pathways. PDGF stimulation indirectly activates a number of additional signaling pathways, such as JNK, p38 and Erk5 MAP-kinase pathways and the small GTP:ases Rac, Rho and Cdc42. All these signaling pathways lead to stimulation of cell proliferation, survival and migration.
References
1.Heldin CH,et al. J Intern Med. 2018;283(1):16–44.