Expression of a transmembrane phosphotyrosine phosphatase inhibits cellular response to platelet-derived growth factor and insulin-like growth factor-1

• Published in: The Journal of biological chemistry Vol. 267; no. 33; pp. 23443 - 23446
• Main Authors: MOONEY, R. A, FREUND, G. G, WAY, B. A, BORDWELL, K. L
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 25-11-1992
• Subjects: Animals; Biological and medical sciences; Cell Division - drug effects; Cell Membrane - metabolism; Cell physiology; Female; Fundamental and applied biological sciences. Psychology; Insulin-Like Growth Factor I - pharmacology; Kinetics; Leukocyte Common Antigens - genetics; Leukocyte Common Antigens - isolation & purification; Leukocyte Common Antigens - metabolism; Mammary Neoplasms, Experimental; Mice; Molecular and cellular biology; Platelet-Derived Growth Factor - pharmacology; Pregnancy; Protein Tyrosine Phosphatases - genetics; Protein Tyrosine Phosphatases - isolation & purification; Protein Tyrosine Phosphatases - metabolism; Recombinant Proteins - isolation & purification; Recombinant Proteins - metabolism; Responses to growth factors, tumor promotors, other factors; Transfection; Tumor Cells, Cultured; Signal transduction; Vertebrata; Membrane receptor; Regulation(control); Mammalia; Somatomedin C; Mouse; Enzyme; Rodentia; Platelet derived growth factor; Protein-tyrosine-phosphatase
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)35854-X

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.