STAM, signal transducing adaptor molecule, is associated with Janus kinases and involved in signaling for cell growth and c-myc induction

Immunity. 1997 Apr;6(4):449-57. doi: 10.1016/s1074-7613(00)80288-5.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*
  • Transfection
  • Tumor Cells, Cultured
  • Tyrosine / metabolism
  • src Homology Domains / genetics
  • src Homology Domains / immunology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Endosomal Sorting Complexes Required for Transport
  • Interleukin-2
  • Phosphoproteins
  • Proto-Oncogene Proteins
  • Receptors, Interleukin-2
  • STAM protein, human
  • Stam protein, mouse
  • Tyrosine
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • DNA
  • Protein-Tyrosine Kinases
  • JAK2 protein, human
  • JAK3 protein, human
  • Jak2 protein, mouse
  • Jak3 protein, mouse
  • Janus Kinase 2
  • Janus Kinase 3