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Papers In Press, published online ahead of print September 8, 2000
Dipartimento di Scienze Biochimiche, Universita di Firenze, Firenze 50134
Corresponding Author: ramponi{at}scibio.unifi.it
The low molecular weight protein tyrosine phosphatase (LMW-PTP) is an enzyme involved in PDGF-induced mitogenesis and cytoskeleton rearrangement. Our previous results demonstrated that LMW-PTP is able to bind and dephosphorylate activated PDGF receptor, thus inhibiting cell proliferation. Recently we have shown that LMW-PTP is specifically phosphorylated by c-Src in a cytoskeleton-associated fraction in response to PDGF, and this phosphorylation increases about 20-fold LMW-PTP activity. LMW-PTP strongly influences cell adhesion, spreading and chemotaxis induced by PDGF stimulation, by regulating the phosphorylation level of p190Rho-GAP, a protein that is able to regulates Rho activity and hence cytoskeleton rearrangement. In the present study we investigate the physiological role of the two LMW-PTP tyrosine phosphorylation sites, using LMW-PTP mutants on tyrosine 131 or 132. We demonstrate that each tyrosine residue is involved in specific LMW-PTP functions. Both of them are phosphorylated during PDGF signalling. Phosphorylation on tyrosine 131 influences mitogenesis, dephosphorylating activated PDGF-R and cytoskeleton rearrangement, acting on p190RhoGAP. Phosphorylation on tyrosine 132 leads to an increase in the strength of cell substrate adhesion, downregulating matrix metallo-proteases expression, through the inhibition of Grb2/MAPK pathway. In conclusion, LMW-PTP tyrosine phosphorylation on both Tyr131 or Tyr132 cooperate to determine a faster and stronger adhesion to extracellular matrix, although these two events may diverge in timing and relative amount.
J. Biol. Chem, 10.1074/jbc.M006375200
Submitted on July 18, 2000
Accepted on September 8, 2000
LMW-PTP controls the rate and the strenght of NIH-3T3 cells adhesion through its phosphorylation on tyrosine 131 or 132
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