Keeping the (kinase) party going: SLP-76 and ITK dance to the beat.
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.
Qi
Qian
Q
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.
August
Avery
A
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
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