Inhibitory tyrosine protein kinase p50csk is associated with protein-tyrosine phosphatase PTP-PEST in hemopoietic and non-hemopoietic cells.
p50(csk) is a cytosolic tyrosine protein kinase expressed in all cell types. Accumulating data show that it inhibits multiple cellular processes, as a consequence of its ability to repress the enzymatic activity of Src family tyrosine protein kinases. We previously demonstrated that, via its Src homology 3 (SH3) domain, Csk is tightly bound to PEP, a protein-tyrosine phosphatase (PTP) exclusively expressed in hemopoietic cells. In this report, we have tested the possibility that Csk also interacts with PTP-PEST, a ubiquitous PTP sharing structural homology with PEP. Our studies revealed that Csk was associated with PTP-PEST in a variety of cell types, including non-hemopoietic cells. This interaction involved the SH3 region of p50(csk) and a proline-rich region (PPPLPERTPESFVLADM) outside the catalytic region of PTP-PEST. Even though both PTP-PEST and PEP were associated with Csk, significant differences were noted between these two PTPs. PTP-PEST, but not PEP, was also complexed with Shc, an adaptor molecule implicated in the Ras pathway. Moreover, PTP-PEST and PEP were found to accumulate primarily in distinct intracellular compartments in cell fractionation studies. In combination, these findings indicated that, like PEP, PTP-PEST is probably involved in Csk-mediated functions in mammalian cells. Moreover, they suggested that the roles of Csk-PTP-PEST and Csk-PEP are likely to be different.
Davidson
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McGill Cancer Centre, McGill University, Montréal, Quebec, Canada H3G 1Y6.
Cloutier
J F
JF
Gregorieff
A
A
Veillette
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A
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D000081247:CSK Tyrosine-Protein Kinase; D002460:Cell Line; D006412:Hematopoietic Stem Cells; D015151:Immunoblotting; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D011233:Precipitin Tests; D011392:Proline; D011485:Protein Binding; D054594:Protein Tyrosine Phosphatase, Non-Receptor Type 12; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013347:Subcellular Fractions; D014018:Tissue Distribution; D018909:src Homology Domains; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D011392:Proline; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; D054594:Protein Tyrosine Phosphatase, Non-Receptor Type 12; D017027:Protein Tyrosine Phosphatases; C516739:Ptpn12 protein, mouse