LMW-PTP exerts a differential regulation on PDGF- and insulin-mediated signaling

Low-molecular-weight protein tyrosine phosphatase (LMW-PTP) is able to spec ifically bind and dephosphorylate activated PDGF and insulin receptors, mod ulating the onset of mitogenic process. LMW-PTP is present in two distinct intracellular locations. While the cytosolic LMW-PTP pool interacts directl y with activated insulin or PDGF receptors, the cytoskeleton-associated LMW -PTP is tyrosine phosphorylated upon PDGF stimulation and is involved in cy toskeleton rearrangement acting on p190Rho-GAP. We investigated the differe ntial role of LMW-PTP in PDGF- or insulin-induced mitogenesis and cytoskele ton rearrangement. Dominant negative LMW-PTP influences both PDGF and insul in-induced mitogenesis with a different extent and it induces a decrease in cellular adhesion and chemotaxis after PDGF but not insulin treatment. PDG F but not insulin stimulation leads to tyrosine phosphorylation of LMW-PTP. We propose that the differential effect of LMW-PTP on PDGF and insulin sig naling is mainly due to the fact that during insulin signaling LMW-PTP does not become phosphorylated and thus does not act on its cytoskeleton-associ ated substrate/s. (C) 2000 Academic Press.