Interaction of SLP adaptors with the SH2 domain of Tec family kinases.
Activation of lymphocytes through their antigen receptors leads to mobilization of intracellular Ca(2+) ions. This process requires expression of SLP adaptors and involves phosphorylation of phospholipase C-gamma isoforms by the Tec-related protein tyrosine kinase Btk in B cells and Itk in T cells. The SH2 domain of Btk and Itk is essential for phospholipase C-gamma phosphorylation and mutations in this domain lead to the X-linked agammaglobulinemia immuno deficiency in humans. Here we show that, in contrast to SH2 domains from other signaling proteins, the Btk and Itk SH2 domains exhibit a restricted binding specificity. They bind selectively to tyrosine-phosphorylated SLP-65 and SLP-76 in activated B and T cells, respectively. Our findings suggest that Btk/Itk and phospholipase C-gamma both bind via their SH2 domain to phosphorylated SLP adaptors, and that this association is required for the activation of phospholipase C-gamma.
Su
Y W
YW
Abteilung für Molekulare Immunologie Biologie III, Universität Freiburg und Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
Zhang
Y
Y
Schweikert
J
J
Koretzky
G A
GA
Reth
M
M
Wienands
J
J
D048868:Adaptor Proteins, Signal Transducing; D000077329:Agammaglobulinaemia Tyrosine Kinase; D001402:B-Lymphocytes / Q000378:metabolism*; D002352:Carrier Proteins; D002460:Cell Line; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000302:isolation & purification / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; C113939:B cell linker protein; D002352:Carrier Proteins; D010750:Phosphoproteins; D011947:Receptors, Antigen, B-Cell; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; C092947:SLP-76 signal Transducing adaptor proteins; D014443:Tyrosine; D005982:Glutathione Transferase; C489300:LTK protein, human; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human