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Constitutive activation of Jak‐2 and Tyk‐2 in a v‐Src‐transformed human gallbladder adenocarcinoma cell line
Author(s) -
Murakami Yoshikazu,
Nakano Shuji,
Niho Yoshiyuki,
Hamasaki Naotaka,
Izuhara Kenji
Publication year - 1998
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199805)175:2<220::aid-jcp12>3.0.co;2-c
Subject(s) - stat4 , proto oncogene tyrosine protein kinase src , transfection , stat3 , signal transduction , phosphorylation , biology , microbiology and biotechnology , tyrosine , tyrosine phosphorylation , tyrosine kinase , jak stat signaling pathway , chemistry , cancer research , stat , cell culture , biochemistry , genetics
It is well known that v‐Src phosphorylates various substrates on tyrosine residue and associates with tyrosine‐phosphorylated proteins as well as proline‐rich ligands through its SH2 and SH3 domains, respectively, thereby inducing oncogenic transformation. A signal pathway from the cell surface to genes in the nucleus, the Jak/STAT (signal transducers and activators of transcription) pathway, has been shown to be involved in the signal transduction mechanism mediated by many cytokines and growth factors. Although a member of the STAT family, STAT3 has been reported to be constitutively activated in several v‐Src‐transformed cells, and it still remains unknown whether Jak molecules, which act upstream of STATs, are involved in the v‐Src‐induced activation mechanism of STAT3. In this study, we analyzed activations of both Jak and STAT molecules using v‐Src‐transformed HAG‐1 cells derived from a human gallbladder adenocarcinoma. STAT3 was found to be constitutively activated in v‐Src‐transformed HAG‐1 cells, but not in either non‐transformed mock‐transfected or activated c‐H‐ras‐transfected HAG‐1 cells, even though the other known STAT molecules are expressed. Furthermore, both Jak‐2 and Tyk‐2 were constitutively activated only in v‐Src‐transformed HAG‐1 cells. Association of v‐Src with either STAT3 or the Jak molecules was not observed. No change of this activation was detected by either interferon (IFN)‐α 2a or IFN‐γ, which had shown inhibitory effects on the growth of v‐Src‐transformed HAG‐1 cells. These results raise the possibility that Jak‐2 and Tyk‐2 are both activated by v‐Src, thereby contributing to the constitutive activation of STAT3 in the v‐Src‐transformed cells. J. Cell. Physiol. 175:220–228, 1998. © 1998 Wiley‐Liss, Inc.