Exposure of cells to H2O2 activates Lck by inducing simultaneous phosphorylation at both Tyr-394 and Tyr-505, indicating that dephosphorylation of Tyr-505 is not required for activation.
In cells exposed to H2O2, Lck activation by Tyr-394 phosphorylation overrides the inhibitory effect of Tyr-505 phosphorylation, a mechanism that may extend to all Src family members.
Members of the Src family of non-receptor tyrosine protein kinases are known to be inhibited by the intramolecular association between a phosphorylated carboxyl-terminal tyrosine residue and the SH2 domain. We have previously shown that exposure of cells to H2O2 strongly activates Lck, a lymphocyte-specific Src family kinase, by inducing phosphorylation on Tyr-394, an absolutely conserved residue within the activation loop of the catalytic domain. Here we show that Lck that has been activated by H2O2 is simultaneously phosphorylated at both the carboxyl-terminal tyrosine (Tyr-505) and Tyr-394. Thus, dephosphorylation of Tyr-505 is not a prerequisite for either phosphorylation of Lck at Tyr-394 or catalytic activation of the kinase. These results indicate that activation of Lck by phosphorylation of Tyr-394 is dominant over any inhibition induced by phosphorylation of Tyr-505. We propose that these results may be extended to all Src family members.
Hardwick et al. (Wed,) reported a other. Hydrogen peroxide (H2O2) was evaluated on Phosphorylation of Lck at Tyr-394 and Tyr-505. Exposure of cells to H2O2 activates Lck by inducing simultaneous phosphorylation at both Tyr-394 and Tyr-505, indicating that dephosphorylation of Tyr-505 is not required for activation.