Physical and functional interactions between receptor-like protein- tyrosine phosphatase α and p59(fyn)

Abstract

We have examined the in vive activity of receptor-like protein-tyrosine phosphatase α (PTPα) toward p59(fyn), a widely expressed Src family kinase. In a coexpression system, PTPα effected a dose-dependent tyrosine dephosphorylation and activation of p59(fyn), where maximal dephosphorylation correlated with a 5-fold increase in kinase activity. PTPα expression resulted in increased accessibility of the p59(fyn) SH2 domain, consistent with a PTPα-mediated dephosphorylation of the regulatory C-terminal tyrosine residue of p59(fyn). No p59(fyn) 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 p59(fyn) underwent association. Reciprocal immunoprecipitations and assays detected p59(fyn) and an appropriate kinase activity in PTPα immunoprecipitates and PTPα and PTP activity in p59(fyn) immunoprecipitates. No association between CD45 and p59(fyn) was detected in similar experiments. The PTPα-mediated activation of p59(fyn) is not prerequisite for association since wild-type and inactive mutant PTPα bound equally well to p59(fyn). Endogenous PTPα and p59(fyn) were also found in association in mouse brain. Together, these results demonstrate a physical and functional interaction of PTPα and p59(fyn) that may be of importance in PTPα-initiated signaling events.