Expression of a transmembrane phosphotyrosine phosphatase inhibits cellular response to platelet-derived growth factor and insulin-like growth factor-1.
Tyrosine phosphorylation is a mechanism of signal transduction shared by many growth factor receptors and oncogene products. Phosphotyrosine phosphatases (PTPases) potentially modulate or counter-regulate these signaling pathways. To test this hypothesis, the transmembrane PTPase CD45 (leukocyte common antigen) was expressed in the murine cell line C127. Hormone-dependent autophosphorylation of the platelet-derived growth factor (PDGF) and insulin-like growth factor-1 (IGF-1) receptors was markedly reduced in cells expressing the transmembrane PTPase. Tyrosine phosphorylation of other PDGF-dependent phosphoproteins (160, 140, and 55 kDa) and IGF-1-dependent phosphoproteins (145 kDa) was similarly decreased. Interestingly, the pattern of growth factor-independent tyrosine phosphorylations was comparable in cells expressing the PTPase and control cells. This suggests a selectivity or accessibility of the PTPase limited to a subset of cellular phosphotyrosyl proteins. The maximum mitogenic response to PDGF and IGF-1 in cells expressing the PTPase was decreased by 67 and 71%, respectively. These results demonstrate that a transmembrane PTPase can both affect the tyrosine phosphorylation state of growth factor receptors and modulate proximal and distal cellular responses to the growth factors.
Mooney
R A
RA
Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, New York 14642.
Freund
G G
GG
Way
B A
BA
Bordwell
K L
KL
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011247:Pregnancy; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases