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. 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.
Takeshita
T
T
Department of Microbiology, Tohoku University School of Medicine, Sendai, Japan.
Arita
T
T
Higuchi
M
M
Asao
H
H
Endo
K
K
Kuroda
H
H
Tanaka
N
N
Murata
K
K
Ishii
N
N
Sugamura
K
K
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D004247:DNA / Q000096:biosynthesis; D056827:Endosomal Sorting Complexes Required for Transport; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D016259:Genes, myc / Q000187:drug effects / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D053614:Janus Kinase 2; D053616:Janus Kinase 3; D051379:Mice; D009154:Mutation; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011518:Proto-Oncogene Proteins; D015375:Receptors, Interleukin-2 / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D018909:src Homology Domains / Q000235:genetics / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D056827:Endosomal Sorting Complexes Required for Transport; D007376:Interleukin-2; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D015375:Receptors, Interleukin-2; C109775:STAM protein, human; C491648:Stam protein, mouse; D014443:Tyrosine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004247:DNA; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; C507933:JAK3 protein, human; C507926:Jak2 protein, mouse; C507935:Jak3 protein, mouse; D053614:Janus Kinase 2; D053616:Janus Kinase 3