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Phospholipase C‐gamma, a substrate for PDGF receptor kinase, is not phosphorylated on tyrosine during the mitogenic response to CSF‐1.
Author(s) -
Downing J.R.,
Margolis B.L.,
Zilberstein A.,
Ashmun R.A.,
Ullrich A.,
Sherr C.J.,
Schlessinger J.
Publication year - 1989
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1989.tb08496.x
Subject(s) - memphis , biology , library science , computer science , botany
Quiescent mouse NIH3T3 cells expressing a transduced human c‐fms gene encoding the receptor for colony stimulating factor‐1 (CSF‐1) were stimulated with mitogenic concentrations of platelet‐derived growth factor (PDGF) or CSF‐1. Immunoprecipitated phospholipase C‐gamma (PLC‐gamma) was phosphorylated on tyrosine and calcium was mobilized following treatment of intact cells with PDGF. In contrast, only trace amounts of phosphotyrosine were incorporated into PLC‐gamma and no intracellular calcium signal was detected after CSF‐1 stimulation. Similarly, CSF‐1 treatment did not stimulate phosphorylation of PLC‐gamma on tyrosine in a CSF‐1‐dependent. SV40‐immortalized mouse macrophage cell line that expresses high levels of the CSF‐1 receptor. In fibroblasts, antiserum to PLC‐gamma co‐precipitated a fraction of the tyrosine phosphorylated form of the PDGF receptor (PDGF‐R) after ligand stimulation, implying that phosphorylated PDGF‐R and PLC‐gamma were associated in a stable complex. Pre‐treatment of cells with orthovanadate also led to tyrosine phosphorylation of PLC‐gamma which was significantly enhanced by PDGF, but not by CSF‐1. Thus, although the PDGF and CSF‐1 receptors are structurally related and appear to be derived from a single ancestor gene, only PDGF‐induced mitogenesis in fibroblasts correlated with tyrosine phosphorylation of PLC‐gamma.