Activation of the colony-stimulating factor 1 receptor leads to the rapid tyrosine phosphorylation of GTPase-activating protein and activation of cellular p21ras.
We have previously reported that platelet-derived growth factor (PDGF) induced tyrosine phosphorylation of GTPase-activating protein (GAP) in intact quiescent fibroblasts under conditions in which insulin and basic fibroblast growth factor (bFGF) were ineffective (Molloy et al., 1988). In the present study, we have provided evidence that colony-stimulating factor 1 (CSF-1) is capable of inducing tyrosine phosphorylation of GAP and its associated cellular proteins, p62 and p190, in NIH3T3 cells overexpressing the human CSF-1 receptor (CSF-1R). However, the extent of GAP tyrosine phosphorylation induced by CSF-1 was approximately 10% of that induced by PDGF-BB in the NIH3T3 fibroblasts. Despite this significant difference, both PDGF-BB and CSF-1 increased the activation of p21ras, the extent of which correlated well with the mitogenic response induced by each growth factor in these cells. Taken together, our findings provide evidence for a possible role of tyrosine phosphorylation of GAP and GAP-associated phosphoproteins in regulating transduction of CSF-1-induced mitogenic signals through p21ras activation.
Heidaran
M A
MA
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892.
Molloy
C J
CJ
Pangelinan
M
M
Choudhury
G G
GG
Wang
L M
LM
Fleming
T P
TP
Sakaguchi
A Y
AY
Pierce
J H
JH
D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D020690:GTPase-Activating Proteins; D005786:Gene Expression Regulation; D011905:Genes, ras; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics*; D017479:Receptors, Platelet-Derived Growth Factor; D020703:ras GTPase-Activating Proteins
D020690:GTPase-Activating Proteins; D010982:Platelet-Derived Growth Factor; D011506:Proteins; D011956:Receptors, Cell Surface; D020703:ras GTPase-Activating Proteins; D016186:Receptor, Macrophage Colony-Stimulating Factor; D017479:Receptors, Platelet-Derived Growth Factor