Low molecular weight protein-tyrosine phosphatase controls the rate and the strength of NIH-3T3 cells adhesion through its phosphorylation on tyrosine 131 or 132.
The low molecular weight protein-tyrosine phosphatase (LMW-PTP) is an enzyme involved in platelet-derived growth factor (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 LMW-PTP activity about 20-fold. 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 regulate 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 signaling. 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, down-regulating matrix metalloproteases expression, through the inhibition of Grb2/MAPK pathway. In conclusion, LMW-PTP tyrosine phosphorylation on both Tyr(131) or Tyr(132) cooperate to determine a faster and stronger adhesion to extracellular matrix, although these two events may diverge in timing and relative amount.
Chiarugi
P
P
Dipartimento di Scienze Biochimiche, Università degli studi di Firenze, 50134 Firenze, Italy.
Taddei
M L
ML
Cirri
P
P
Talini
D
D
Buricchi
F
F
Camici
G
G
Manao
G
G
Raugei
G
G
Ramponi
G
G
D016475:3T3 Cells; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D051379:Mice; D008970:Molecular Weight; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism*
D010982:Platelet-Derived Growth Factor; D014443:Tyrosine; D017027:Protein Tyrosine Phosphatases