SHP-2 can suppress transformation induced by platelet-derived growth factor.
Signaling by either the type alpha or type beta receptors of platelet-derived growth factor occurs by phosphorylation of at least 10 intra-cytoplasmic tyrosine residues and their subsequent association of secondary signaling molecules with Src homology 2 (SH2) domains. Although the role of several of these secondary signaling molecules in mitogenesis has become increasingly clear, their roles in morphological transformation are not as well defined. Here we present evidence that the SHP-2 phosphatase which associates with Tyr 1009 of the type beta receptor and Tyr 720 of the type alpha receptor may suppress transformation induced by the PDGF B chain. Cotransfection of a dominant negative mutant of the SHP-2 gene and the PDGF B chain gene into mouse fibroblasts that only poorly formed foci with the PDGF B chain alone resulted in larger and more prominent foci. Furthermore, introduction of a wild-type copy of the SHP-2 gene into a tumor cell line, U-87MG, which relies on PDGF expression to form foci in vitro, caused a reversion of phenotype.
Jazayeri
A
A
Wayne State University, Detroit, Michigan 48202, USA.
McGee
J
J
Shimamura
T
T
Cross
S B
SB
Bejcek
B E
BE
D016475:3T3 Cells; D000818:Animals; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D046911:Macromolecular Substances; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000502:physiology*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured; D018909:src Homology Domains
D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; D020928:Mitogen-Activated Protein Kinases; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse; C509248:Ptpn6 protein, mouse; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases