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.
Takahashi-Tezuka
M
M
Department of Molecular Oncology, Biomedical Research Center, Osaka University Medical School, Suita, Japan.
Hibi
M
M
Fujitani
Y
Y
Fukada
T
T
Yamaguchi
T
T
Hirano
T
T
D015703:Antigens, CD / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002461:Cell Line, Transformed; D006801:Humans; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051567:Proto-Oncogene Proteins c-vav; D018123:Receptors, Interleukin / Q000378:metabolism*; D016185:Receptors, Interleukin-3 / Q000378:metabolism*; D019947:Receptors, Interleukin-6
D015703:Antigens, CD; D018797:Cell Cycle Proteins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D018123:Receptors, Interleukin; D016185:Receptors, Interleukin-3; D019947:Receptors, Interleukin-6; C496618:VAV1 protein, human; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2