Regulation of Lck by rafts and Cbp. Cbp is localized to rafts in resting cells, where it is phosphorylated by active Lck*, an Src family PTK. This modification recruits Csk, which inactivates Lck† by phosphorylating its C-terminal regulatory site, and PEP, which dephosphorylates the Lck activation loop. Another phosphatase, CD45, is localized outside the rafts but may have access to Lck at the lateral boundary or during rare meetings due to partitioning into the same membrane domain. Activation of the TCR results in dephosphorylation of Cbp through the action of an unidentified phosphatase, thus removing the inhibitory complex containing Csk and PEP.