LMW-PTP exerts a differential regulation on PDGF- and insulin-mediated signaling.
Low-molecular-weight protein tyrosine phosphatase (LMW-PTP) is able to specifically bind and dephosphorylate activated PDGF and insulin receptors, modulating the onset of mitogenic process. LMW-PTP is present in two distinct intracellular locations. While the cytosolic LMW-PTP pool interacts directly with activated insulin or PDGF receptors, the cytoskeleton-associated LMW-PTP is tyrosine phosphorylated upon PDGF stimulation and is involved in cytoskeleton rearrangement acting on p190Rho-GAP. We investigated the differential role of LMW-PTP in PDGF- or insulin-induced mitogenesis and cytoskeleton rearrangement. Dominant negative LMW-PTP influences both PDGF- and insulin-induced mitogenesis with a different extent and it induces a decrease in cellular adhesion and chemotaxis after PDGF but not insulin treatment. PDGF but not insulin stimulation leads to tyrosine phosphorylation of LMW-PTP. We propose that the differential effect of LMW-PTP on PDGF and insulin signaling is mainly due to the fact that during insulin signaling LMW-PTP does not become phosphorylated and thus does not act on its cytoskeleton-associated substrate/s.
Taddei
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ML
Dipartimento di Scienze Biochimiche, Università di Firenze, Viale Morgagni 50, Florence, 50134, Italy.
Chiarugi
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Manao
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Raugei
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Ramponi
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D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects; D003599:Cytoskeleton / Q000201:enzymology; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D008938:Mitosis / Q000187:drug effects; D008970:Molecular Weight; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014443:Tyrosine / Q000378:metabolism
D007328:Insulin; D010982:Platelet-Derived Growth Factor; D014443:Tyrosine; D017027:Protein Tyrosine Phosphatases