Tyrosine phosphorylation of CD6 by stimulation of CD3: augmentation by the CD4 and CD2 coreceptors.
When T cells are activated via the T cell receptor (TCR) complex a number of cellular substrates, including some cell surface proteins, become phosphorylated on tyrosine (Tyr) residues. Phosphorylation of cytoplasmic Tyr renders these cell surface receptors competent to interact with proteins that link cell surface receptors to protein in the intracellular signaling pathways. Here we show that Tyr residues in the cytoplasmic domain of CD6 become phosphorylated upon T cell activation via the TCR complex. Tyr phosphorylation was observed when the T cells were activated by crosslinking CD3 or by cocrosslinking CD3 with CD2 or CD4, but not when the cells were stimulated by crosslinking CD2, CD4, or CD28 alone. Unlike other Tyr kinase substrates, such as the phospholipase C gamma 1-associated pp35/36 protein, whose level of Tyr phosphorylation is highest when T cells are activated by cocrosslinking CD3 with CD2, the levels of CD6 Tyr phosphorylation are highest when T cells were activated by cocrosslinking CD3 with CD4.
Wee
S
S
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
Schieven
G L
GL
Kirihara
J M
JM
Tsu
T T
TT
Ledbetter
J A
JA
Aruffo
A
A
D015703:Antigens, CD / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism* / Q000502:physiology*; D018801:CD2 Antigens; D017252:CD3 Complex / Q000502:physiology*; D015704:CD4 Antigens / Q000502:physiology*; D018956:CD5 Antigens; D006801:Humans; D008213:Lymphocyte Activation; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011971:Receptors, Immunologic / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology; D014443:Tyrosine / Q000378:metabolism*
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D015704:CD4 Antigens; D018956:CD5 Antigens; C062279:CD6 antigen; D011971:Receptors, Immunologic; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases