Tec tyrosine kinase links the cytokine receptors to PI-3 kinase probably through JAK.

Tec/Btk tyrosine kinases are members of a subgroup of Src tyrosine kinase family. They are reported to be activated in response to cytokines, such as IL-3 and IL-6. Janus kinases (JAKs) are known to associate with certain cytokine receptors, e.g. gp130, the signal transducing subunit of IL-6 receptor, and the ...
common beta chain of IL-3 receptor, which can be activated upon receptor dimerization in response to cytokines. Here we show the association between Jak1/Jak2 and Tec or Jak1 and Btk. Furthermore, Jak1 but not Jak2 induces tyrosine phosphorylation of Btk, but not Tec. These observations suggest that upon cytokine stimulation JAKs activate Tec/Btk or induce their dimerization resulting in endogenous tyrosine phosphorylation. Furthermore using a yeast two-hybrid system we have identified the target molecules for Tec, the p85 and p55PIK subunits of PI-3 kinase, and Vav. Tec associated with Vav through its SH2 domain independently of its kinase activity. In contrast the p85 and p55PIK subunits of PI-3 kinase associated with the SH2-kinase domain of Tec, dependent on Tec kinase activity. Consistent with these, IL-6 or IL-3 induced the association between Tec and the p85 subunit of PI-3 kinase in mammalian cells. These findings suggest that Tec tyrosine kinase links cytokine receptors to PI-3 kinase probably through JAKs.
Mesh Terms:
1-Phosphatidylinositol 3-Kinase, Antigens, CD, Cell Cycle Proteins, Cell Line, Transformed, Humans, Janus Kinase 1, Janus Kinase 2, Phosphotransferases (Alcohol Group Acceptor), Protein Binding, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-vav, Receptors, Interleukin, Receptors, Interleukin-3, Receptors, Interleukin-6
Oncogene
Date: May. 15, 1997
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