Low M(r) phosphotyrosine protein phosphatase interacts with the PDGF receptor directly via its catalytic site.
Many proteins bind to the activated platelet derived growth factor receptor (PDGF-R) either directly or by means of adapter molecules. Up to now all these proteins were shown to transmit and amplify the signal started with PDGF-R stimulation. In a recent study our group had demonstrated that low M(r) phosphotyrosine protein phosphatase (LMW-PTP) specifically interacts with PDGF-R in NIH3T3 cells. In the present study we have attempted to clarify the modality of interaction, both in vivo and in vitro, of these two proteins, using a catalytically inactive LMW-PTP mutant. Our results indicate that LMW-PTP and PDGF-R interact directly, without the necessity of any adapter protein. This interaction leads to PDGF-R dephosphorylation and, presumably, interrupts one or more of the mitogenic pathways that originate from receptor activation.
Chiarugi
P
P
Departimento di Scienze Biochimiche di Firenze, Università di Firenze, Italy.
Cirri
P
P
Raugei
G
G
Manao
G
G
Taddei
L
L
Ramponi
G
G
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D008961:Models, Structural; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010710:Phosphates / Q000494:pharmacology; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D014162:Transfection; D014638:Vanadates / Q000494:pharmacology
D004791:Enzyme Inhibitors; D010710:Phosphates; D011993:Recombinant Fusion Proteins; D014638:Vanadates; D017479:Receptors, Platelet-Derived Growth Factor; D017027:Protein Tyrosine Phosphatases