title: Keeping the (kinase) party going: SLP-76 and ITK dance to the beat.
abstract: The Tec-family protein tyrosine kinase IL-2-inducible T cell kinase (ITK) mediates T cell activation, as does the adaptor protein SLP-76 (SH2-domain-containing leukocyte protein of 76 kD), which forms a complex with ITK and other intracellular signaling enzymes. One of these enzymes is phospholipase C-gamma1 (PLC-gamma1), which mediates T cell receptor (TCR)-stimulated intracellular calcium mobilization leading to the activation of transcription factors such as nuclear factor of activated T cells. The Src-family tyrosine kinase Lck and the Syk-family tyrosine kinase zeta chain-associated protein kinase of 70 kD (ZAP-70), together with ITK, are necessary for the phosphorylation of PLC-gamma1 in response to TCR stimulation. ITK is thought to phosphorylate a specific tyrosine residue of PLC-gamma1 that is required for its activation. The mechanism of activation of ITK appears to involve the interaction between SLP-76 and ITK, which not only initiates ITK activity but is also important to maintain the kinase activity of ITK. This suggests that SLP-76 acts as more than a neutral adaptor in mediating T cell activation; SLP-76 also directly influences the kinase activity of ITK, allowing ITK to phosphorylate PLC-gamma1.
authors.affiliation: Center for Molecular Immunology and Infectious Disease, Immunology and Infectious Disease Graduate Program, and Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Qi
authors.forename: Avery
authors.initials: A
authors.lastname: August
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D008213:Lymphocyte Activation / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology; D046912:Multiprotein Complexes; D051966:Phospholipase C gamma / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry / Q000502:physiology*; D010766:Phosphorylation; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000502:physiology; D015290:Second Messenger Systems / Q000502:physiology; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C110810:LAT protein, human; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; C092947:SLP-76 signal Transducing adaptor proteins; D015544:Inositol 1,4,5-Trisphosphate; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; C080813:emt protein-tyrosine kinase; C522157:PLCG1 protein, human; D051966:Phospholipase C gamma