Abstract
The protein-tyrosine phosphatase SHP-1 has been shown to be a negative regulator of multiple signaling pathways in hematopoietic cells. In this study, we demonstrate that SHP-1 dephosphorylates the lymphoid-specific Src family kinase Lck at Tyr-394 when both are transiently co-expressed in nonlymphoid cells. We also demonstrate that a GST-SHP-1 fusion protein specifically dephosphorylates Lck at Tyr-394 in vitro. Because phosphorylation of Tyr-394 activates Lck, the fact that SHP-1 specifically dephosphorylates this site suggests that SHP-1 is a negative regulator of Lck. The failure of SHP-1 to inactivate Lck may contribute to some of the lymphoid abnormalities observed in motheaten mice.
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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Catalytic Domain
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Cell Line
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Humans
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Intracellular Signaling Peptides and Proteins
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / chemistry
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism*
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Phosphorylation
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases / chemistry
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Protein Tyrosine Phosphatases / metabolism*
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Tyrosine / metabolism*
Substances
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Intracellular Signaling Peptides and Proteins
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Tyrosine
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
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PTPN6 protein, human
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases