PMID: 7523375Oct 7, 1994Paper

Inhibition of p21ras activation blocks proliferation but not differentiation of interleukin-3-dependent myeloid cells.

The Journal of Biological Chemistry
K OkudaJ D Griffin

Abstract

Interleukin-3 (IL-3) induces proliferation of immature myeloid cells and mast cells and prevents programmed cell death (apoptosis) in vitro. These activities are exerted through binding of IL-3 to specific, high affinity receptors that then initiate a series of intracellular signaling events. Among the earliest of these signaling events in an IL-3-dependent cell line such as 32Dcl3 are activation of one or more receptor-associated tyrosine kinases followed by activation of p21ras. In an effort to define the functional role of p21ras activation in mediating the effects of IL-3, we constructed a series of sublines of 32Dcl3 in which a dominant inhibitory mutant of Ha-ras (c-Ha-ras(Asn-17)) was expressed under the control of a steroid-inducible promoter. Steroid treatment (dexamethasone, 1 microM) specifically induced c-Ha-ras(Asn-17) protein and mRNA and blocked IL-3-induced accumulation of p21ras-GTP in 32Dcl3/p21rasN17 cell lines, but not in control cells. Dexamethasone slightly inhibited IL-3-dependent proliferation of control 32Dcl3 cell lines (to 80% of maximum), but it completely blocked proliferation of 32Dcl3/p21rasN17 cell lines and induced cell cycle arrest in G0/G1. This proliferative block could be overcome by cotrans...Continue Reading

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