STAM, Signal Transducing Adaptor Molecule, Is Associated with Janus Kinases and Involved in Signaling for Cell Growth and c- myc Induction

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. ST...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 1997-04, Vol.6 (4), p.449-457
Main Authors: Takeshita, Toshikazu, Arita, Tomikazu, Higuchi, Masaya, Asao, Hironobu, Endo, Kazuhiro, Kuroda, Hiroshi, Tanaka, Nobuyuki, Murata, Kazuko, Ishii, Naoto, Sugamura, Kazuo
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing
Animals
Cell Division - genetics
Cell Division - immunology
DNA - biosynthesis
Endosomal Sorting Complexes Required for Transport
Gene Expression Regulation - drug effects
Gene Expression Regulation - immunology
Genes, myc - drug effects
Genes, myc - immunology
Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology
Humans
Interleukin-2 - pharmacology
Janus Kinase 2
Janus Kinase 3
Mice
Mutation
Phosphoproteins - metabolism
Phosphorylation
Protein-Tyrosine Kinases - genetics
Protein-Tyrosine Kinases - metabolism
Protein-Tyrosine Kinases - physiology
Proto-Oncogene Proteins
Receptors, Interleukin-2 - genetics
Signal Transduction - genetics
Signal Transduction - immunology
src Homology Domains - genetics
src Homology Domains - immunology
Transfection
Tumor Cells, Cultured
Tyrosine - metabolism
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Summary: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.
ISSN:1074-7613
1097-4180
DOI:10.1016/S1074-7613(00)80288-5