Regulated association between the tyrosine kinase Emt/Itk/Tsk and phospholipase-C gamma 1 in human T lymphocytes.
The Emt/Itk/Tsk tyrosine kinase is involved in intracellular signaling events induced by several lymphocyte surface receptors. Modulation of TCR/CD3-induced phospholipase-C gamma 1 (PLC gamma 1) activity by the tyrosine kinase Emt/Itk/Tsk has been demonstrated based on studies of Itk-deficient murine T lymphocytes. Here we report a TCR/CD3-regulated association between Emt and PLC gamma 1 in both normal and leukemic T cells. In addition, this association was enhanced following independent ligation of the CD2, CD4, or CD28 costimulatory molecules, but not of CD5 or CD6 surface receptors, correlating to the induced tyrosine phosphorylation of Emt. Before Ab-induced T cell activation, we found that the Emt-SH3 domain was crucial for the constitutive Emt/PLC gamma 1 association; however, upon TCR/CD3 engagement, the Emt-SH2 domain was more efficient in mediating the enhanced Emt/PLC gamma 1 interaction. Furthermore, the PLC gamma 1-SH3 domain, but not the two PLC gamma 1-SH2 domains, contributed to formation of the protein complex. Thus, we describe a regulated interaction between Emt and PLC gamma 1, and based on our studies with individual Emt and PLC gamma 1 SH2/SH3 domains, we propose a mechanism for this association.
Perez-Villar
J J
JJ
Immunology, Inflammation, and Pulmonary Drug Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543, USA. perezvillar@bms.com
Kanner
S B
SB
D018801:CD2 Antigens / Q000276:immunology / Q000378:metabolism; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism / Q000502:physiology*; D019169:Jurkat Cells; D008024:Ligands; D051966:Phospholipase C gamma; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology*; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism / Q000502:physiology; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D010738:Type C Phospholipases / Q000378:metabolism / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism; D018909:src Homology Domains / Q000276:immunology
D018801:CD2 Antigens; D018106:CD28 Antigens; D015704:CD4 Antigens; D007527:Isoenzymes; D008024:Ligands; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase; D010738:Type C Phospholipases; D051966:Phospholipase C gamma