Low molecular weight protein-tyrosine phosphatase tyrosine phosphorylationby c-Src during platelet-derived growth factor-induced mitogenesis correlates with its subcellular targeting

The low molecular weight phosphotyrosine phosphatase (LMW-PTP) is an enzyme that is involved in the early events of platelet-derived growth factor (PD GF) receptor signal transduction, Our previous results have shown that LMW- PTP is able to specifically bind and dephosphorylate activated PDGF recepto r, thus modulating PDGF-induced mitogenesis, In particular LMW-PTP is invol ved in pathways that regulate the transcription of the immediately early ge nes myc and fos in response to growth factor stimulation. In this study we have established that, in nontransformed NIH3T3 cells, LMW-PTP exists const itutively in cytosolic and cytoskeleton-associated localization and that, a fter PDGF stimulation, c-Src is able to bind and to phosphorylate LMW-PTP o nly in the cytoskeleton-associated fraction. As a consequence of its tyrosi ne phosphorylation, LMW-PTP significantly increases its catalytic activity, After PDGF stimulation these two LMW-PTP pools act on distinct substrates, contributing in different manners to the PDGF receptor signaling, The cyto plasmic LMW-PTP fraction exerts its well known action on activated PDGF rec eptor. On the other hand we have now demonstrated that the cytoskeleton-ass ociated LMW-PTP acts specifically on a few not yet identified proteins that become tyrosine-phosphorylated in response to the PDGF receptor activation . Finally, these two LMW-PTP pools markedly differ in the timing of the pro cesses in which they are involved. The cytoplasmic LMW-PTP pool exerts its action within a few minutes from PDGF receptor activation (short term actio n), while tyrosine phosphorylation of cytoskeleton-associated LMW-PTP lasts for more than 40 min (long term action). In conclusion LMW-PTP is a striki ng example of an enzyme that exerts different functions and undergoes diffe rent regulation in consequence of its subcellular localization.