SHP-2 can suppress transformation induced by platelet-derived growth factor

Signaling by either the type alpha or type beta receptors of platelet-deriv ed 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 o f these secondary signaling molecules in mitogenesis has become increasingl y clear, their roles in morphological transformation are not as well define d. Here we present evidence that the SHP-2 phosphatase which associates wit h 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 int o mouse fibroblasts that only poorly formed foci with the PDGF B chain alon e resulted in larger and more prominent foci. Furthermore, introduction of a wildtype copy of the SHP-2 gene into a tumor cell line, U-87MG, which rel ies on PDGF expression to form foci in vitro, caused a reversion of phenoty pe. (C) 2000 Academic Press.