Cytoskeletal Protein PSTPIP1 Directs the PEST-Type Protein Tyrosine Phosphatase to the c-Abl Kinase to Mediate Abl Dephosphorylation

A search for c-Abl interacting proteins resulted in the recovery of PSTPIP1, originally identified as a binding protein of the PEST-type protein tyrosine phosphatases (PTP). PSTPIP1 was phosphorylated by c-Abl, and growth factor–induced PSTPIP1 phosphorylation was diminished in Abl null fibroblasts....

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Bibliographic Details
Published in:Molecular cell 2000-12, Vol.6 (6), p.1413-1423
Main Authors: Cong, Feng, Spencer, Susan, Côté, Jean-François, Wu, Yan, Tremblay, Michel L, Lasky, Laurence A, Goff, Stephen P
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing
Animals
c-Abl protein
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cells, Cultured
COS Cells
Cytoskeletal Proteins - genetics
Cytoskeletal Proteins - metabolism
dephosphorylation
Enzyme Activation - drug effects
Epitopes
Macromolecular Substances
Mice
Mutation
Phosphorylation - drug effects
Phosphotyrosine - metabolism
Platelet-Derived Growth Factor - pharmacology
Protein Binding
Protein Tyrosine Phosphatase, Non-Receptor Type 12
Protein Tyrosine Phosphatases - chemistry
Protein Tyrosine Phosphatases - genetics
Protein Tyrosine Phosphatases - metabolism
Proto-Oncogene Proteins c-abl - genetics
Proto-Oncogene Proteins c-abl - metabolism
src Homology Domains
Substrate Specificity
Transfection
Two-Hybrid System Techniques
Yeasts
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Summary:A search for c-Abl interacting proteins resulted in the recovery of PSTPIP1, originally identified as a binding protein of the PEST-type protein tyrosine phosphatases (PTP). PSTPIP1 was phosphorylated by c-Abl, and growth factor–induced PSTPIP1 phosphorylation was diminished in Abl null fibroblasts. PSTPIP1 was able to bridge c-Abl to the PEST-type PTPs. Several experiments suggest that the PEST-type PTPs negatively regulate c-Abl activity: c-Abl was hyperphosphorylated in PTP-PEST–deficient cells; disruption of the c-Abl–PSTPIP1–PEST-type PTP ternary complex by overexpression of PSTPIP1 mutants increased c-Abl phosphotyrosine content; and PDGF-induced c-Abl kinase activation was prolonged in PTP-PEST–deficient cells. Dephosphorylation of c-Abl by PEST-type PTP represents a novel mechanism by which c-Abl activity is regulated.
ISSN:1097-2765
1097-4164
DOI:10.1016/S1097-2765(00)00138-6