References
Query Results -- Details
MGI Accession ID: MGI:3850655
J Number: J:150402
Other Accession IDs:
Title: p56(dok-2) as a cytokine-inducible inhibitor of cell proliferation and signal transduction.
Authors: Suzu S; Tanaka-Douzono M; Nomaguchi K; Yamada M; Hayasawa H; Kimura F; Motoyoshi K
Journal: EMBO J
Volume: 19
Issue: 19
Date: 2000 Oct 2
Year: 2000
Pages: 5114-22
Review Status: Peer Reviewed
Abstract:
p56(dok-2) acts as a multiple docking protein downstream of receptor or non-receptor tyrosine kinases. However, the role of p56(dok-2) in biological functions of cells is not clear. We found that transcription of the p56(dok-2) gene in macrophages was increased markedly in response to cytokines such as macrophage colony-stimulating factor (M-CSF), granulocyte/macrophage-CSF and interleukin-3 (IL-3). Forced expression of p56(dok-2) inhibited M-CSF-, granulocyte-CSF-, IL-3- and stem cell factor-induced proliferation of myeloid leukemia cells, M-NFS-60. The p56(dok-2)-overexpressing cells showed an impaired induction of c-myc but not of c-jun, junB or c-fos when stimulated with M-CSF. Consistent with these results, the peritoneal cavity of the hairless (hr/hr) strain of mutant mice, whose cells expressed less p56(dok-2) than wild-type mice, contained more macrophages than that of +/hr mice. Moreover, the inhibition of endogenous p56(dok-2) expression in macrophage-like tumor cells, J774A.1, by stable expression of antisense p56(dok-2) mRNA accelerated cell proliferation. The study identifies a novel role for p56(dok-2) as a molecule that negatively regulates signal transduction and cell proliferation mediated by cytokines in a feedback loop.
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