The cytoskeleton-associated TCR zeta chain is constitutively phosphorylated in the absence of an active p56(lck) form

The TCR recognizes peptide-MHC complexes and transmits activation signals l eading to cellular responses. We have previously characterized two TCR popu lations expressed on the T cell surface; one is linked to the cytoskeleton via a detergent-insoluble cytoskeleton-associated zeta (cska-zeta) chain, w hile the other is detergent soluble and not linked to the cytoskeleton. The cska-zeta form displays unique properties: it is constitutively phosphoryl ated, does not undergo hyperphosphorylation upon TCR stimulation as opposed to its noncytoskeleton-associated counterpart (non-cska-zeta) and it maint ains a molecular mass of 16 kDa. It is well established that p56(lck) and p ossibly p59(fyn) are responsible for the generation of the 21/23-kDa phosph orylated detergent-soluble zeta form. We now demonstrate that the phosphory lation of cska-zeta does not require the activity of p56(lc)k. We also show that although Lck does not phosphorylate cska-zeta in vivo, it retains the capacity to phosphorylate cska-zeta in vitro. Moreover, differences in zet a -associated kinase activity were detected for non-cska-zeta and cska-zeta . Our results indicating that different kinases phosphorylate the two zeta forms are consistent with a growing consensus that each TCR form may regula te distinct cellular functions.