CD28 ligation induces rapid tyrosine phosphorylation of the linker molecule LAT in the absence of Syk and ZAP-70 tyrosine phosphorylation.
CD28 is a T cell surface molecule that is important for T cell activation. CD28-triggered T cell stimulation involves protein tyrosine phosphorylation, a process that is critical for CD28 function. Recently, a linker molecule has been identified as LAT (Linker for Activation of T cells). Studies involving LAT mutants and reconstitution experiments strongly implicate LAT in playing a critical role in T cell activation. We show in the present report that CD28 ligation induces tyrosine phosphorylation of LAT. CD28-induced tyrosine phosphorylation of LAT was rapid, as it was apparent within 1 min of CD28 ligation, reached a peak by 5 min, and declined thereafter. Previous studies implicated the protein tyrosine kinases ZAP-70 and Syk in the TCR-induced tyrosine phosphorylation of LAT. Here, tyrosine phosphorylation of Syk and ZAP-70 was detected after TCR but not after CD28 ligation. Thus, CD28 ligation appears to induce tyrosine phosphorylation of LAT by mechanisms that are independent of ZAP-70 and Syk. The concurrent ligation of CD28 and TCR increased tyrosine phosphorylation of LAT. These results implicate LAT in CD28 signal transduction pathways and in the co-stimulatory process in T cells.
Tsuchida
M
M
Department of Surgery, University of Wisconsin, Madison 53792, USA.
Manthei
E R
ER
Knechtle
S J
SJ
Hamawy
M M
MM
D048868:Adaptor Proteins, Signal Transducing; D018106:CD28 Antigens / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D004792:Enzyme Precursors / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008565:Membrane Proteins; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D000072377:Syk Kinase; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D051746:ZAP-70 Protein-Tyrosine Kinase
D048868:Adaptor Proteins, Signal Transducing; D018106:CD28 Antigens; D002352:Carrier Proteins; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; C110810:LAT protein, human; D008565:Membrane Proteins; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human