Inducible T cell tyrosine kinase regulates actin-dependent cytoskeletal events induced by the T cell antigen receptor.
The tec family kinase, inducible T cell tyrosine kinase (Itk), is critical for both development and activation of T lymphocytes. We have found that Itk regulates TCR/CD3-induced actin-dependent cytoskeletal events. Expression of Src homology (SH) 2 domain mutant Itk transgenes into Jurkat T cells inhibits these events. Furthermore, Itk(-/-) murine T cells display significant defects in TCR/CD3-induced actin polymerization. In addition, Jurkat cells deficient in linker for activation of T cells expression, an adaptor critical for Itk activation, display impaired cytoskeletal events and expression of SH3 mutant Itk transgenes reconstitutes this impairment. Interestingly, expression of an Itk kinase-dead mutant transgene into Jurkat cells has no effect on cytoskeletal events. Collectively, these data suggest that Itk regulates TCR/CD3-induced actin-dependent cytoskeletal events, possibly in a kinase-independent fashion.
Grasis
Juris A
JA
Department of Biology and Molecular Biology Institute, San Diego State University, San Diego, CA 92182, USA.
Browne
Cecille D
CD
Tsoukas
Constantine D
CD
D000199:Actins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D048868:Adaptor Proteins, Signal Transducing; D019943:Amino Acid Substitution / Q000235:genetics / Q000276:immunology; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis; D003599:Cytoskeleton / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D016297:Mutagenesis, Site-Directed; D010750:Phosphoproteins / Q000096:biosynthesis / Q000172:deficiency; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D018909:src Homology Domains / Q000235:genetics / Q000276:immunology
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C110810:LAT protein, human; C491734:Lat protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase