TY - JOUR
T1 - STAM, signal transducing adaptor molecule, is associated with janus kinases and involved in signaling for cell growth and c-myc induction
AU - Takeshita, Toshikazu
AU - Arita, Tomikazu
AU - Higuchi, Masaya
AU - Asao, Hironobu
AU - Endo, Kazuhiro
AU - Kuroda, Hiroshi
AU - Tanaka, Nobuyuki
AU - Murata, Kazuko
AU - Ishii, Naoto
AU - Sugamura, Kazuo
N1 - Funding Information:
We thank Drs. J. Miyazaki, H. Ariga, K. Arai, S. Nagata, J. N. Ihle, A. Miyajima, M. Yamamoto, Y. Nabeshima, J. J. O'Shea, and T. Taniguchi for providing us with pCXN2 plasmid, pHXCAT plasmid, plasmids for human GM-CSF receptor α and βc genes, pEF-BOS plasmid, Prk5Jak1 and Prk5Jak3 plasmids, pEF-BOSJak2 plasmid, pME-lck plasmid, pENL plasmid, anti-Jak3 antibody, and the BAF-B03 cell line, respectively. We also thank Dr. S. Watanabe for her valuable suggestions and Dr. S. Moffatt for critically reading the manuscript. This work was supported in part by CREST (Core Research for Evolutional Science and Technology) of the Japan Science and Technology Corporation (JST), a grant-in-aid for scientific research on priority areas from the Ministry of Education, Science, Sports, and Culture of Japan, a grant-in-aid from the Ministry of Health and Welfare of Japan for the comprehensive 10 year strategy for cancer control, a grant from special coordination funds of the Science and Technology Agency of Japan, and a grant from the Inamori Foundation.
PY - 1997/4/1
Y1 - 1997/4/1
N2 - We previously identified a putative signal transducing adaptor molecule, named STAM, that contains an Src homology 3 (SH3) domain and immunoreceptor tyrosine-based activation motif (ITAM). In this report, we demonstrate the functional significance of STAM in cytokine-mediated signal transduction. STAM is associated with Jak3 and Jak2 tyrosine kinases via its ITAM region and phosphorylated by Jak3 and Jak2 upon stimulation with IL-2 and GM-CSF, respectively. An SH3 deletion mutant of STAM confers a dominant negative effect on DNA synthesis mediated by IL-2 and GM-CSF. Furthermore, the wild-type STAM, but not STAM mutants deleted of SH3 and ITAM, significantly enhances c-myc induction mediated by IL-2 and GM-CSF. These results strongly implicate STAM in the signaling pathways for cell growth and c-myc induction immediately downstream of the Jaks associated with the cytokine receptors.
AB - We previously identified a putative signal transducing adaptor molecule, named STAM, that contains an Src homology 3 (SH3) domain and immunoreceptor tyrosine-based activation motif (ITAM). In this report, we demonstrate the functional significance of STAM in cytokine-mediated signal transduction. STAM is associated with Jak3 and Jak2 tyrosine kinases via its ITAM region and phosphorylated by Jak3 and Jak2 upon stimulation with IL-2 and GM-CSF, respectively. An SH3 deletion mutant of STAM confers a dominant negative effect on DNA synthesis mediated by IL-2 and GM-CSF. Furthermore, the wild-type STAM, but not STAM mutants deleted of SH3 and ITAM, significantly enhances c-myc induction mediated by IL-2 and GM-CSF. These results strongly implicate STAM in the signaling pathways for cell growth and c-myc induction immediately downstream of the Jaks associated with the cytokine receptors.
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U2 - 10.1016/S1074-7613(00)80288-5
DO - 10.1016/S1074-7613(00)80288-5
M3 - Article
C2 - 9133424
AN - SCOPUS:17044444647
SN - 1074-7613
VL - 6
SP - 449
EP - 457
JO - Immunity
JF - Immunity
IS - 4
ER -
