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 leading to cellular responses. We have previously characterized two TCR populations expressed on the T cell surface; one is linked to the cytoskeleton via a detergent-insoluble cytoskeleton-associated zeta (cska-zeta) chain, while the other is detergent soluble and not linked to the cytoskeleton. The cska-zeta form displays unique properties: it is constitutively phosphorylated, does not undergo hyperphosphorylation upon TCR stimulation as opposed to its non-cytoskeleton-associated counterpart (non-cska-zeta) and it maintains a molecular mass of 16 kDa. It is well established that p56(lck) and possibly p59(fyn) are responsible for the generation of the 21/23-kDa phosphorylated detergent-soluble zeta form. We now demonstrate that the phosphorylation of cska-zeta does not require the activity of p56(lck). 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 zeta-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 regulate distinct cellular functions.
Caplan
S
S
Cell Biology and Metabolism Branch, National Institute of Child health and Human Development, National Institutes of Health, Bethesda, USA.
Almogi-Hazan
O
O
Ezernitchi
A
A
Manaster
E
E
Gazit
A
A
Baniyash
M
M
D000818:Animals; D003599:Cytoskeleton / Q000737:chemistry*; D005260:Female; D007526:Isoelectric Point; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*
D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)