Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Animals
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COS Cells
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cells, Cultured
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism*
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Enzyme Activation / drug effects
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Epitopes
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Macromolecular Substances
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Mice
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Mutation
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Phosphorylation / drug effects
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Phosphotyrosine / metabolism
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Platelet-Derived Growth Factor / pharmacology
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Protein Binding
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Protein Tyrosine Phosphatase, Non-Receptor Type 12
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Protein Tyrosine Phosphatases / chemistry
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Protein Tyrosine Phosphatases / genetics
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Protein Tyrosine Phosphatases / metabolism*
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Proto-Oncogene Proteins c-abl / genetics
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Proto-Oncogene Proteins c-abl / metabolism*
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Substrate Specificity
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Transfection
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Two-Hybrid System Techniques
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Yeasts
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src Homology Domains
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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Cytoskeletal Proteins
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Epitopes
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Macromolecular Substances
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Platelet-Derived Growth Factor
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Pstpip1 protein, mouse
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Phosphotyrosine
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Proto-Oncogene Proteins c-abl
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Protein Tyrosine Phosphatase, Non-Receptor Type 12
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Protein Tyrosine Phosphatases
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Ptpn12 protein, mouse