Hrs is associated with STAM, a signal-transducing adaptor molecule. Its suppressive effect on cytokine-induced cell growth

We previously reported a new type of signal-transducing adaptor molecule, STAM, which was shown to be involved in cytokine-mediated intracellular signal transduction. In this study, we molecularly cloned a 110-kDa phosphotyrosine protein inducible by stimulation with interleukin 2 (IL-2). The 110-kD...

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Bibliographic Details
Published in:The Journal of biological chemistry 1997-12, Vol.272 (52), p.32785-32791
Main Authors: Asao, H, Sasaki, Y, Arita, T, Tanaka, N, Endo, K, Kasai, H, Takeshita, T, Endo, Y, Fujita, T, Sugamura, K
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing
Animals
Cell Line
Chromosome Banding
Cloning, Molecular
COS Cells
DNA Replication
Endosomal Sorting Complexes Required for Transport
Granulocyte-Macrophage Colony-Stimulating Factor - metabolism
Humans
Interleukin-2 - metabolism
Janus Kinase 2
Janus Kinase 3
Mice
Molecular Sequence Data
Molecular Weight
Phosphoproteins - genetics
Phosphoproteins - metabolism
Phosphorylation
Protein-Tyrosine Kinases - metabolism
Proto-Oncogene Proteins
Signal Transduction
src Homology Domains
Zinc Fingers
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Summary:We previously reported a new type of signal-transducing adaptor molecule, STAM, which was shown to be involved in cytokine-mediated intracellular signal transduction. In this study, we molecularly cloned a 110-kDa phosphotyrosine protein inducible by stimulation with interleukin 2 (IL-2). The 110-kDa molecule was found to be a human counterpart of mouse Hrs (hepatocyte growth factor-regulated tyrosine kinase substrate) and to be associated with STAM. Tyrosine phosphorylation of Hrs is induced rapidly after stimulation with IL-2 and granulocyte-macrophage colony-stimulating factor as well as hepatocyte growth factor. The mutual association sites of Hrs and STAM include highly conserved coiled-coil sequences, suggesting that their association is mediated by the coiled-coil structures. Exogenous introduction of the wild-type Hrs significantly suppressed DNA synthesis upon stimulation with IL-2 and granulocyte-macrophage colony-stimulating factor, while the Hrs mutant deleted of the STAM-binding site lost such suppressive ability. These results suggest that Hrs counteracts the STAM function which is critical for cell growth signaling mediated by the cytokines.
ISSN:0021-9258
DOI:10.1074/jbc.272.52.32785