Kun-Liang Guan, Ph.D. | Institute of Gerontology

Research Professor, IoG
Professor of Biological Chemistry
Medical School

5450 Med. Sci. I Bldg.
Ann Arbor, MI 48109-0606
Tel: (734) 763-3030
Fax: (734) 763-4581
Email: kunliang@umich.edu

Research in my laboratory focuses on cellular signal transduction pathways involved in cell growth regulation, cancer biology, and neurobiology. We have been investigating the molecular activation mechanism of the Ras-MAP kinase pathway. A major project in my laboratory is to understand how cell growth and cell size are coordinately regulated by growth factors, nutrients, and cellular energy levels. TSC1 and TSC2 are tumor suppressor genes, where mutations in those genes are responsible for the inherited genetic disease tuberous sclerosis complex (TSC). Rheb is a member of the Ras superfamily small GTPases. mTOR is the mammalian target of rapamycin and has protein kinase activity. We are studying the role of TSC-Rheb-mTOR pathways in regulation of protein synthesis; hence cell growth and cell size control. The other major project in my laboratory is to study protein tyrosine kinases and Rho family small GTPases in neuronal axon guidance receptor signaling. We are particularly interested in the semaphorin receptor plexin and the netrin receptor DCC and Unc5.

Publications

Inoki, K., Li, Y., Zhu, T., Wu, J. and Guan, K-L. (2002) TSC2 is phosphorylated and inhibited by AKT and suppresses mTOR signaling. Nature Cell Biol. 4, 648-657.

Aurandt, J., Vikis, H.G., Gutkind, S., Ahn, N., and Guan, K-L. (2002) The semaphorin receptor plexin-B1 signals through a direct interaction with the Rho specific nucleotide exchange factor, LARG. Proc. Natl. Acad. Sci. USA 99, 12085-12090.

Li, Y., Inoki, K., Vacrasis, P., and Guan, K-L. (2003) The p38 and MK2 kinase cascade phosphorylates tuberin, the tuberous sclerosis 2 (TSC2) gene product, and enhances its interaction with 14-3-3. J. Biol. Chem. 278, 13663-13671.

Inoki, K., Li, Y., Xu, T., and Guan, K-L. (2003) Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes & Development, 17, 1829-1834.

Tang, E.D., Wang, C., Xiong, Y., and Guan, K-L. (2003) A role for NEMO/IKK? ubiquitination in activation of I?B kinase complex by TNFa. J. Biol. Chem. 278, 37297-305.

Inoki, K., Zhu, T., and Guan, K-L. (2003) TSC2 mediates cellular energy response to control cell growth and survival. Cell 115, 577-590.

Li., W. and Guan, K-L. (2004) The Down syndrome cell adhesion molecule DSCAM interacts with and activates PAK. J. Biol. Chem. 279, 32824-31.
Corradetti, M., Inoki, K., Bardeesy, N., DePinho R., and Guan, K-L. (2004) Regulation of the TSC pathway by LKB1: Evidence of a molecular link between Tuberous Sclerosis Complex and Peutz-Jeghers Syndrome. Genes & Dev. 18, 533-1538.

Li, W., Lee, J., Vikis, H., et al, and Guan, K-L. Activation of FAK and Src are receptor proximal events required for netrin signaling. Nature Neurosci. (in press).

Li, Y., Inoki, K., and Guan, K-L. (2004) Biochemical and functional characterization of small GTPase Rheb and TSC2 GAP activity. Mol. Cell. Biol. 24, 7695-75.