Low molecular weight protein-tyrosine phosphatase is involved in growth inhibition during cell differentiation.
Low molecular weight protein-tyrosine phosphatase (LMW-PTP) is an enzyme involved in mitogenic signaling and cytoskeletal rearrangement after platelet-derived growth factor (PDGF) stimulation. Recently, we demonstrated that LMW-PTP is regulated by a redox mechanism involving the two cysteine residues of the catalytic site, which turn reversibly from reduced to oxidized state after PDGF stimulation. Since recent findings showed a decrease of intracellular reactive oxygen species in contact inhibited cells and a lower tyrosine phosphorylation level in dense cultures in comparison to sparse ones, we studied if the level of endogenous LMW-PTP is regulated by growth inhibition conditions, such as cell confluence and differentiation. Results show that both cell confluence and cell differentiation up-regulate LMW-PTP expression in C2C12 and PC12 cells. We demonstrate that during myogenesis LMW-PTP is regulated at translational level and that the protein accumulates at the plasma membrane. Furthermore, we showed that both myogenesis and cell-cell contact lead to a dramatic decrease of tyrosine phosphorylation level of PDGF receptor. In addition, we observed an increased association of the receptor with LMW-PTP during myogenesis. Herein, we demonstrate that myogenesis decreases the intracellular level of reactive oxygen species, as observed in dense cultures. As a consequence, LMW-PTP turns from oxidized to reduced form during muscle differentiation, increasing its activity in growth inhibition conditions such as differentiation. These data suggest that LMW-PTP plays a crucial role in physiological processes, which require cell growth arrest such as confluence and differentiation.
Fiaschi
T
T
Dipartimento di Scienze Biochimiche, Universita' degli Studi di Firenze, 50134 Firenze, Italy.
Chiarugi
P
P
Buricchi
F
F
Giannoni
E
E
Taddei
M L
ML
Talini
D
D
Cozzi
G
G
Zecchi-Orlandini
S
S
Raugei
G
G
Ramponi
G
G
D000818:Animals; D000077214:Becaplermin; D002452:Cell Count; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D018613:Microscopy, Confocal; D008970:Molecular Weight; D024510:Muscle Development / Q000502:physiology; D010084:Oxidation-Reduction; D016716:PC12 Cells; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D015854:Up-Regulation
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D017382:Reactive Oxygen Species; D000077214:Becaplermin; D017479:Receptors, Platelet-Derived Growth Factor; D017027:Protein Tyrosine Phosphatases