Abstract
p62dok has been identified as a substrate of many oncogenic tyrosine kinases such as the chronic myelogenous leukemia (CML) chimeric p210bcr-abl oncoprotein. It is also phosphorylated upon activation of many receptors and cytoplamic tyrosine kinases. However, the biological functions of p62dok in normal cell signaling as well as in p210bcr-abl leukemogenesis are as yet not fully understood. Here we show, in hemopoietic and nonhemopoietic cells derived from p62dok-/- mice, that the loss of p62dok results in increased cell proliferation upon growth factor treatment. Moreover, Ras and mitogen-activated protein kinase (MAPK) activation is markedly sustained in p62dok-/- cells after the removal of growth factor. However, p62dok inactivation does not affect DNA damage and growth factor deprivation-induced apoptosis. Furthermore, p62dok inactivation causes a significant shortening in the latency of the fatal myeloproliferative disease induced by retroviral-mediated transduction of p210bcr-abl in bone marrow cells. These data indicate that p62dok acts as a negative regulator of growth factor-induced cell proliferation, at least in part through downregulating Ras/MAPK signaling pathway, and that p62dok can oppose leukemogenesis by p210bcr-abl.
Original language | English (US) |
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Pages (from-to) | 275-284 |
Number of pages | 10 |
Journal | Journal of Experimental Medicine |
Volume | 194 |
Issue number | 3 |
DOIs | |
State | Published - Aug 6 2001 |
Externally published | Yes |
Keywords
- Cell proliferation
- Knockout
- Mast cells
- Signal transduction
- Thymocytes
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology