Involvement of ras p21 protein in signal-transduction pathways from interleukin 2, interleukin 3, and granulocyte/macrophage colony-stimulating factor, but not from interleukin 4.

Abstract

The protooncogene ras acts as a component of signal-transduction networks in many kinds of cells. The ras gene product (p21) is a GTP-binding protein, and the activity of the protein is regulated by bound GDP/GTP. Recent studies have shown that a certain class of growth factors stimulates the formation of active p2lFGTP complexes in fibroblasts and that oncogene products with enhanced tyrosine kinase activities have a similar effect on ras p21. We have measured the ratio of active GTP-bound p21 to total p21 in several lymphoid and myeloid cell lines in order to understand the role of ras in the proliferation of these cells. Interleukin 2 (IL-2), IL-3, and granulocyte/macrophage colony-stimulating factor (GM-CSF) enhance the formation of the active p21GTP, whereas IL4 has no effect on p21-bound GDP/GTP. These results strongly suggest that ras p21 acts as a transducer of signals from IL-2, IL-3, and GM-CSF, but not from IL-4.

IL-3 signaling and the role of Src kinases, JAKs and STATs: a covert liaison unveiled

“…Upon recruitment, Shc binds to the phosphorylated Y577 of the b c subunit and subsequently interacts with the adaptor protein Grb2, which in turn associates with mSos, which is the nucleotide exchange factor for Ras (Pratt et al, 1996;Rozakis-Adcock et al, 1993). This is followed by the activation of Ras and c-Raf (Pazdrak et al, 1995;Co er et al, 1998a,b;Satoh et al, 1991). The activation of Ras and c-Raf results in downstream activation of ERK1 and ERK2 that are members of the MAP kinase family (Pazdrak et al, 1995;Raines et al, 1992;Okuda et al, 1992;Welham et al, 1992;Co er et al, 1998a,b).…”

“…The activation of Ras and c-Raf results in downstream activation of ERK1 and ERK2 that are members of the MAP kinase family (Pazdrak et al, 1995;Raines et al, 1992;Okuda et al, 1992;Welham et al, 1992;Co er et al, 1998a,b). Activation of this cascade culminates in the increased expression of transcription factors c-fos and c-jun (Itoh et al, 1996;Satoh et al, 1991Satoh et al, , 1993.…”

Effective reversal of a transformed phenotype by retrovirus-mediated transfer of a ribozyme directed against mutant N-ras

“…1 In hemopoiesis, the importance of Ras is indicated by its involvement in the signaling pathways activated by the majority of hemopoietic growth factors. 2,3 Ras functions as a molecular switch in signal transduction and is active when in the GTP-bound state and inactive when the bound GTP is hydrolyzed to GDP. Oncogenic Ras mutations generally result in severe impairment of Ras GTPase activity and thus stimulate cell growth or differentiation autonomously.…”

HMG-I(Y) Phosphorylation Status as a Nuclear Target Regulated through Insulin Receptor Substrate-1 and the I4R Motif of the Interleukin-4 Receptor

“…However, Ras, Raf, and mitogen-activated protein kinase activation by IL-4 have been undetectable in many (although not all) cell types and thus are less consistently crucial to IL-4R function relative to most members of the hematopoietin receptor superfamily (57)(58)(59)(60). Accordingly, it is unlikely that mitogen-activated protein kinase-like pathways contribute substantially to regulation of IL-4 function through Stat6.…”