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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

UT-7 is a human megakaryoblastic cell line capable of growing in interleukin-3, granulocyte-macrophage colony-stimulating factor, or erythropoietin (Epo) (Cancer Res 51:341, 1991). We used this cell line and a selected Epo-dependent subcell line (UT-7/Epo) to study the early signal transduction events induced by Epo. When UT-7 cells were exposed to Epo, tyrosine phosphorylation of several proteins (with molecular weight equivalent to that of p85, p110, and p145) was observed. Protein phosphorylation occurred in both a dose- and time-dependent manner. p85 showed a marked increase in phosphotyrosine content within 30 seconds; maximal phosphorylation was observed at 1 minute. Subsequently, tyrosine phosphorylation of p110 and p145 was observed, beginning at 1 minute and reaching plateau at 5 minutes. The degree of phosphorylation of these three proteins gradually decreased thereafter. In addition, in UT-7/Epo cells, Epo induced tyrosine phosphorylation of other proteins that were not observed in Epo-induced UT-7 cells. The concentration of Epo required to induce tyrosine phosphorylation was in the same range of concentration required to stimulate cell growth. Epo was also able to activate p21ras as measured by exchange of guanosine diphosphate for guanosine triphosphate. These data show that tyrosine phosphorylation and P21ras activation are early signals in the Epo-induced mitogenic pathway.
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PMID:Erythropoietin rapidly induces tyrosine phosphorylation in the human erythropoietin-dependent cell line, UT-7. 137 53

Phosphatidylinositol 3-kinase (PI3-kinase) is a cytosolic enzyme that plays key roles in mediating signaling through many receptors. The heterodimeric form of PI3-kinase is made up of a regulatory subunit, p85, and a catalytic subunit, p110. Although granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to activate PI3-kinase, the mechanisms by which this activation is mediated and regulated are incompletely understood. Here we show that treatment of human neutrophils with GM-CSF induced both time- and concentration-dependent increases in the level of tyrosine phosphorylation of p85. The ability of GM-CSF to activate PI3-kinase was abolished by pretreating the cells with erbstatin, a tyrosine kinase inhibitor. The simultaneous treatment of the cells with GM-CSF and phorbol esters such as phorbol 12-myristate 13-acetate (PMA) and phorbol 12,13-dibutyrate (PDBu) significantly inhibited both the tyrosine phosphorylation of p85 and the activation of PI3-kinase. The inhibitory effects of phorbol esters were not induced by their inactive analogues and they were selective to the stimulation of tyrosine phosphorylation of p85 since phorbol esters did not alter the enhancement of the pattern of tyrosine phosphorylation of other cellular proteins, including that of Jak2 induced by GM-CSF. However, PMA significantly inhibited the in situ tyrosine phosphorylation and the activation of lyn observed in response to GM-CSF. The results suggest that the activation of PI3-kinase by GM-CSF is mediated by the tyrosine phosphorylation of p85 and that this activation is downregulated by PKC possibly via the inhibition of lyn.
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PMID:Granulocyte-macrophage colony-stimulating factor-activated signaling pathways in human neutrophils. I. Tyrosine phosphorylation-dependent stimulation of phosphatidylinositol 3-kinase and inhibition by phorbol esters. 902 36