The low M-r protein-tyrosine phosphatase is involved in Rho-mediated cytoskeleton rearrangement after integrin and platelet-derived growth factor stimulation

The low molecular weight protein-tyrosine phosphatase (LMW-PTP) is an enzym e that is involved in the early events of platelet-derived growth factor (P DGF) receptor signal transduction, In fact, LMW-PTP is able to specifically bind and dephosphorylate activated PDGF receptor, thus modulating PDGF-ind uced mitogenesis. In particular, LMW-PTP is involved in pathways that regul ate the transcription of the immediately early genes myc and fos in respons e to growth factor stimulation. Recently, we have found that LMW-PTP exists constitutively in cytosolic and cytoskeleton-associated localization and t hat, after PDGF stimulation, c-Src is able to bind and phosphorylate LMW-PT P only in the cytoskeleton-associated fraction. As a consequence of its pho sphorylation, LMW-PTP increases its catalytic activity about 20-fold, In th is study, our interest was to investigate the role of LMW-PTP phosphorylati on in cellular response to PDGF stimulation, To address this issue, we have transfected in NIH-3T3 cells a mutant form of LMW-PTP in which the c-Src p hosphorylation sites (Tyr(131) and Tyr(132)) were mutated to alanine, We ha ve established that LMW-PTP phosphorylation by c-Src after PDGF treatment s trongly influences both cell adhesion and migration. In addition, we have d iscovered a new LMW-PTP substrate localized in the cytoskeleton that become s tyrosine-phosphorylated after PDGF treatment: p190Rho-GAP, Hence, LMW-PTP plays multiple roles in PDGF receptor-mediated mitogenesis, since it can b ind and dephosphorylate PDGF receptor, and, at the same time, the cytoskele ton-associated LMW-PTP, through the regulation of the p190Rho-GAP phosphory lation state, controls the cytoskeleton rearrangement in response to PDGF s timulation.