A kinase independent function for Tec kinase ITK in regulating antigen receptor induced serum response factor activation. 2006

Shengli Hao, and Qian Qi, and Jianfang Hu, and Avery August
Department of Veterinary and Biomedical Sciences, Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, 115 Henning Building, University Park, 16802, USA.

The Tec family kinases are critical downstream regulators of antigen receptor signals in lymphocytes. As kinases, they act on critical substrates to regulate signals such as calcium increase leading to activation of transcription factors such as NFAT, NFkappaB and SRF. We now show here that ITK, a member of the Tec family of tyrosine kinases, has a kinase independent function. Mutants of ITK that lack kinase activity or a kinase domain can rescue cells lacking Tec family kinases for antigen receptor induced SRF activation, but not for NFAT, AP-1 or NFkappaB activation. Furthermore, expression of these mutants in WT cells enhanced SRF activation. This kinase independent function required the SH2 domain since a mutant lacking both the kinase and SH2 domains was much less effective at rescuing SRF activation. This kinase-deleted mutant could partially rescue ERK activation, and interact with multiple tyrosine phosphorylated proteins during antigen receptor signaling, suggesting that ITK uses a scaffolding function that regulates signals leading to specific regulation of SRF activation.

UI MeSH Term Description Entries
D011505 Protein-Tyrosine Kinases Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors. Tyrosine Protein Kinase,Tyrosine-Specific Protein Kinase,Protein-Tyrosine Kinase,Tyrosine Kinase,Tyrosine Protein Kinases,Tyrosine-Specific Protein Kinases,Tyrosylprotein Kinase,Kinase, Protein-Tyrosine,Kinase, Tyrosine,Kinase, Tyrosine Protein,Kinase, Tyrosine-Specific Protein,Kinase, Tyrosylprotein,Kinases, Protein-Tyrosine,Kinases, Tyrosine Protein,Kinases, Tyrosine-Specific Protein,Protein Kinase, Tyrosine-Specific,Protein Kinases, Tyrosine,Protein Kinases, Tyrosine-Specific,Protein Tyrosine Kinase,Protein Tyrosine Kinases,Tyrosine Specific Protein Kinase,Tyrosine Specific Protein Kinases
D011946 Receptors, Antigen Molecules on the surface of B- and T-lymphocytes that recognize and combine with specific antigens. Antigen Receptors,Antigen Receptor,Receptor, Antigen
D002417 Cattle Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor. Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002645 Chickens Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA. Gallus gallus,Gallus domesticus,Gallus gallus domesticus,Chicken
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor
D016328 NF-kappa B Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA. Immunoglobulin Enhancer-Binding Protein,NF-kappa B Complex,Nuclear Factor kappa B,Transcription Factor NF-kB,kappa B Enhancer Binding Protein,Ig-EBP-1,NF-kB,NF-kappaB,Nuclear Factor-Kappab,Complex, NF-kappa B,Enhancer-Binding Protein, Immunoglobulin,Factor NF-kB, Transcription,Factor-Kappab, Nuclear,Ig EBP 1,Immunoglobulin Enhancer Binding Protein,NF kB,NF kappa B Complex,NF kappaB,NF-kB, Transcription Factor,Nuclear Factor Kappab,Transcription Factor NF kB
D050778 NFATC Transcription Factors A family of transcription factors characterized by the presence of highly conserved calcineurin- and DNA-binding domains. NFAT proteins are activated in the CYTOPLASM by the calcium-dependent phosphatase CALCINEURIN. They transduce calcium signals to the nucleus where they can interact with TRANSCRIPTION FACTOR AP-1 or NF-KAPPA B and initiate GENETIC TRANSCRIPTION of GENES involved in CELL DIFFERENTIATION and development. NFAT proteins stimulate T-CELL activation through the induction of IMMEDIATE-EARLY GENES such as INTERLEUKIN-2. NFAT Transcription Factor 1,NFAT Transcription Factor 2,NFAT Transcription Factor 3,NFAT Transcription Factor 4,NFAT Transcription Factor 5,Nuclear Factors of Activated T-Cells,NF-AT Proteins,NF-AT3 Protein,NF-AT4 Protein,NF-ATc1 Protein,NFAT Proteins,NFAT-1 Protein,NFAT-2 Protein,NFAT1 Protein,NFAT2 Protein,NFAT3 Protein,NFAT4 Protein,NFAT5 Protein,NFATC Proteins,NFATC1 Protein,NFATC1 Transcription Factor,NFATC2 Protein,NFATC2 Transcription Factor,NFATC3 Protein,NFATC3 Transcription Factor,NFATC4 Protein,NFATC4 Transcription Factor,NFATL1 Protein,NFATx Protein,NFATz Protein,Nuclear Factor of Activated T-Cells 5 Protein,Nuclear Factor of Activated T-Cells, Cytoplasmic,Nuclear Factor of Activated T-Cells, Cytoplasmic 1 Protein,Nuclear Factor of Activated T-Cells, Cytoplasmic 2 Protein,Nuclear Factor of Activated T-Cells, Cytoplasmic 3 Protein,Nuclear Factor of Activated T-Cells, Cytoplasmic 4 Protein,OREBP Protein,Osmotic Response Element Binding Protein,TonEBP Protein,Tonicity-Responsive Enhancer-Binding Protein,Transcription Factor NF-AT,Factor, NFATC1 Transcription,Factor, NFATC2 Transcription,Factor, NFATC3 Transcription,NF AT Proteins,NF AT3 Protein,NF AT4 Protein,NF ATc1 Protein,NF-AT, Transcription Factor,NFAT 1 Protein,NFAT 2 Protein,Nuclear Factor of Activated T Cells 5 Protein,Nuclear Factor of Activated T Cells, Cytoplasmic,Nuclear Factor of Activated T Cells, Cytoplasmic 1 Protein,Nuclear Factor of Activated T Cells, Cytoplasmic 2 Protein,Nuclear Factor of Activated T Cells, Cytoplasmic 3 Protein,Nuclear Factor of Activated T Cells, Cytoplasmic 4 Protein,Nuclear Factors of Activated T Cells,Tonicity Responsive Enhancer Binding Protein,Transcription Factor NF AT,Transcription Factor, NFATC1,Transcription Factor, NFATC2,Transcription Factor, NFATC3,Transcription Factor, NFATC4,Transcription Factors, NFATC

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