Abstract
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 b 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 induce tyrosine phosphorylation of Btk, but not Tec. These observations suggest that upon cytokine stimulation JAKs activate Tec/Btk or induced their dimerization resulting in endogenous tyrosine phosphorylation. Furthermore using the yeast two-hybrid system we have identified the target molecules for Tec, p85 and p55PIK subunits of PI-3 kinase, and Vav. Tec associated with Vav through its SH2 domain independently of its kinase activity. Whereas p85 and p55PIK subunits of PI-3 kinase associated with the SH2-kinase domain of Tec dependently of Tec kinase activity. Consistent with these, IL-6 or IL-3 induced the association of Tec and p85/p55 subunits. These findings show that Tec-type tyrosine kinases link cytokine receptors to various effector molecules such as Vav and PI-3 kinase probably through JAKs.
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