Src-induced activation of inducible T cell kinase (ITK) requires phosphatidylinositol 3-kinase activity and the pleckstrin homology domain of inducible T cell kinase Journal Article
| Authors: | August, A.; Sadra, A.; Dupont, B.; Hanafusa, H. |
| Article Title: | Src-induced activation of inducible T cell kinase (ITK) requires phosphatidylinositol 3-kinase activity and the pleckstrin homology domain of inducible T cell kinase |
| Abstract: | The Tec family of tyrosine kinases are involved in signals emanating from cytokine receptors, antigen receptors, and other lymphoid cell surface receptors. One family member, ITK (inducible T cell kinase), is involved in T cell activation and can be activated by the T cell receptor and the CD28 cell surface receptor. This stimulation of tyrosine phosphorylation and activation of ITK can be mimicked by the Src family kinase Lck. We have explored the mechanism of this requirement for Src family kinases in the activation of ITK. We found that coexpression of ITK and Src results in increased membrane association, tyrosine phosphorylation and activation of ITK, which could be blocked by inhibitors of the lipid kinase phosphatidylinositol 3-kinase (PI 3-kinase) as well as overexpression of the p85 subunit of PI 3-kinase. Removal of the Pleckstrin homology domain (PH) of ITK resulted in a kinase that could no longer be induced to localize to the membrane or be activated by Src. The PH of ITK was also able to bind inositol phosphates phosphorylated at the D3 position. Membrane targeting of ITK without the PH recovered its ability to be activated by Src. These results suggest that ITK can be activated by a combination of Src and PI 3-kinase. |
| Keywords: | controlled study; nonhuman; t lymphocyte; blood proteins; animal cell; animals; mice; models, biological; enzyme activation; transfection; protein tyrosine kinase; cos cells; phosphorylation; phosphatidylinositol 3 kinase; t lymphocyte receptor; enzyme phosphorylation; recombinant fusion proteins; enzyme inhibitors; 1-phosphatidylinositol 3-kinase; chromones; morpholines; phosphoproteins; mutagenesis, site-directed; protein-tyrosine kinases; monkey; src-family kinases; t lymphocyte activation; cd28 antigen; enzyme induction; phosphotyrosine; proto-oncogene proteins pp60(c-src); pleckstrin; priority journal; article; src homology domains |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 94 |
| Issue: | 21 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 1997-10-14 |
| Start Page: | 11227 |
| End Page: | 11232 |
| Language: | English |
| DOI: | 10.1073/pnas.94.21.11227 |
| PUBMED: | 9326591 |
| PROVIDER: | scopus |
| PMCID: | PMC23424 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
