CELL BIOLOGY AND METABOLISM
Physical and Functional Interactions between Receptor-like Protein-tyrosine Phosphatase α and p59fyn*

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We have examined the in vivo activity of receptor-like protein-tyrosine phosphatase α (PTPα) toward p59fyn, a widely expressed Src family kinase. In a coexpression system, PTPα effected a dose-dependent tyrosine dephosphorylation and activation of p59fyn, where maximal dephosphorylation correlated with a 5-fold increase in kinase activity. PTPα expression resulted in increased accessibility of the p59fyn SH2 domain, consistent with a PTPα-mediated dephosphorylation of the regulatory C-terminal tyrosine residue of p59fyn. No p59fyn dephosphorylation was observed with an enzymatically inactive mutant form of PTPα or with another receptor-like PTP, CD45. Many enzyme-linked receptors are complexed with their substrates, and we examined whether PTPα and p59fyn underwent association. Reciprocal immunoprecipitations and assays detected p59fyn and an appropriate kinase activity in PTPα immunoprecipitates and PTPα and PTP activity in p59fyn immunoprecipitates. No association between CD45 and p59fyn was detected in similar experiments. The PTPα-mediated activation of p59fyn is not prerequisite for association since wild-type and inactive mutant PTPα bound equally well to p59fyn. Endogenous PTPα and p59fyn were also found in association in mouse brain. Together, these results demonstrate a physical and functional interaction of PTPα and p59fyn that may be of importance in PTPα-initiated signaling events.

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This work was supported by the National Science and Technology Board of Singapore.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.