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| Cytokine Receptor Signal Transduction and Regulation of Cell Growth | ||||||
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The growth of myeloid and lymphoid blood cells is governed by cytokine growth factors acting through cell surface receptors. These receptors function through activation of Jak tyrosine kinases, which phosphorylate components of signaling pathways controlling cell survival and proliferation. Blood cell development fails in the absence of Jak kinase activation resulting in anemias, whereas enhanced Jak kinase activity contributes to myeloid and lymphoid leukemias. Work in our laboratory is directed at defining mechanism by which cytokines regulated blood cell growth.
A major focus of work in our laboratory is to define the role of a recently identified ubiquitin ligase, RUL, in regulating Jak kinase activity, and test the concept that competing ubiquitination between a promoter (e.g., RUL) and inhibitor (e.g., SOCS1) regulates the activity of Jak kinases in vivo. This concept represents a novel paradigm in the regulation of signal transduction by mediators of ubiquitination. A second focus of work in our laboratory is to define signaling pathways that control cell cycle progression. In recent work, we have identified a conection between a PI3K signaling pathway and activation of Cdk2, which promotes G1 phase progression in cytokine-dependent hematopoietic cells. |
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| Selected Publications | ||||||
| Click Here for a Complete List of Articles | ||||||
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Lei, H. and Quelle F.W. FOXO transcription factors enforce cell cycle checkpoints and promote survival of hematopoietic cells after DNA damage. Molecular Cancer Research, in press, 2009.
Nimbalkar, D. and Quelle F.W. PI3-kinase signaling overrides a G2 phase arrest checkpoint and promotes aberrant cell cycling and death of hematopoietic cells after DNA damage. Cell Cycle, 7:2877-2885, 2008. Chakravarti, P., Henry, M.K. and Quelle F.W. Prolactin and heregulin override DNA damage-induced growth arrest and promote phosphatidylinositol-3 kinase-dependent proliferation in breast cancer cells. Int. J. Oncol. 26(2):509-14, 2005. Henry, M.K., Nimbalkar, D., Hohl, R.J. and Quelle F.W. Cytokine-induced phosphoinositide 3-kinase activity promotes Cdk2 activation in factor-dependent hematopoietic cells. Exp. Cell Res. 299(1):257-66, 2004. Friedman, A.D., Nimbalkar, D. and Quelle F.W. Erythropoietin receptors associate with a ubiquitin ligase, p33RUL, and require its activity for erythropoietin-induced proliferation. J. Biol. Chem. 278(29):26851-26861, 2003. |
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| Department/Program Affiliations |
| Pharmacology |
| Biosciences |
| Immunology |