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Your search keyword '"Lilly, Michael"' showing total 6 results
Start Over Author "Lilly, Michael" Journal journal of biological chemistry
6 results on '"Lilly, Michael"'

5. The Cytoplasmic Domain of Granulocyte-Macrophage Colony-stimulating Factor (GM-CSF) Receptor α Subunit Is Essential for Both GM-CSF-mediated Growth and Differentiation*

Author

Matsuguchi, Tetsuya, Zhao, Yanming, Lilly, Michael B., and Kraft, Andrew S.

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) regulates differentiation, survival, and proliferation of colony-forming unit-granulocyte-macrophage progenitor cells. The biologic actions of GM-CSF are mediated by binding to a specific receptor consisting of two chains designated as α and β subunits. We have demonstrated that the murine FDC-P1-derived cell line WT-19 transfected with the human GM-CSF receptor α and β subunits (GM-CSFRα and β) can be induced to differentiate by the addition of human GM-CSF (hGM-CSF). By expressing a series of GM-CSFRα mutants in WT19 cells, we have determined the amino acid domains of the GM-CSFRα cytoplasmic domain that regulate cell differentiation, proliferation, and survival. We found that the membrane proximal proline-rich domain and adjacent 16 residues are essential for both hGM-CSF-dependent cell proliferation and differentiation. In contrast, the C-terminal region of the GM-CSFRα cytoplasmic domain was not necessary for cell differentiation mediated by hGM-CSF, but the removal of this region severely impaired the ability of hGM-CSF to support cell survival. While the activation of JAK2, Shc, Erk, and STAT5 proteins correlated with hGM-CSF-mediated cell growth, cellular differentiation occurred in the absence of activation of these signal transduction pathways.

Published
1997
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6. The PIM-2 Kinase Phosphorylates BAD on Serine 112 and Reverses BAD-induced Cell Death.

Author

Bin Yan, Zemskova, Marina, Holder, Sheldon, Chin, Vernon, Kraft, Andrew, Koskinen, Paivi J., and Lilly, Michael

Subjects
*PHOSPHORYLATION, *HEMATOPOIESIS, *BLOOD cells
Abstract

Hematopoietic growth factors mediate the survival and proliferation of blood-forming cells, but the mechanisms through which these proteins produce their effects are incompletely known. Recent studies have identified the pim family of kinases as mediators of cytokinedependent survival signals. Several studies have identified substrates for the pim-1 kinase, but little is known about the other family members, pim-2 and pim-3. We have investigated potential functions for the pim-2 kinase in factor-dependent murine hematopoietic cells. We find that pim-2 mRNA and protein expression are regulated by cytokines similarly to pim-1. Three PIM-2 protein isoforms are produced in cytokinetreated cells. All three forms are active kinases, and the short (PIM-2(34 kDa)) form is the most active at enhancing survival of FDCP1 cells after cytokine withdrawal. This pro-survival function involves inhibition of apoptosis and caspase activation. Enforced expression of PIM2(34 kDa) kinase does not appear to regulate expression of BCL-2, BCL-xL, BIM, or BAX proteins. However, the kinase can phosphorylate the pro-apoptotic protein BAD on serine 112, which accounts in part for its ability to reverse Bad-induced cell death. Our results indicate that pim-2 functions similarly to pim-1 as a pro-survival kinase and suggest that BAD is a legitimate PIM-2 substrate. [ABSTRACT FROM AUTHOR]

Published
2003
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