Zhijun Luo, M.D., Ph.D.

Molecular Mechanisms in Insulin Action and Resistance

The research interests of my lab focus on insulin action and insulin resistance. An ongoing research project is the elucidation of the mechanism by which Raf is activated by vRas, insulin and growth factors. Our second project is to examine the role of AMPK in regulation of energy homeostasis in adipocytes and explore its relationship with insulin signal transduction. In addition, we are interested in the regulation of glucose, fatty acid and protein metabolisms by AMPK in cancer cells such as prostate cancer cells.

References:

1. Kurowski TG, Lin Y, Luo ZJ, Tschlis PN, Buse MG, Heydrick SJ, and Ruderman N. Hyperglycemia inhibits insulin activation of AKT/protein kinase B but not phosphatidylinositol 3-kinase in Raf skeletal muscle. Diabetes 48, 1999.

2. Tzivion G, Luo ZJ, and Avruch, J. Calyculin A induced vimentin phosphorylation sequesters 14-3-3 and displaces other 14-3-3 partners in vivo. J. Biol. Chem. 275: 29772-29778, 2000.

3. Lenz G, Gottfried C, Luo Z, Avruch J, Rodnight R, Nie WJ, Kang Y, and Neary JT. P2Y purinoceptor subtypes recruit different Mek activators in astrocytes. British J. Pharmacology 129: 927-936, 2000.

4. Hayne C, Tzivion G, and Luo Z. Raf-1/MEK/MAPK pathway is necessary for the G2/M transition induced by nocodazole. J. Biol. Chem. 275:31876-31882, 2000.

5. Lenz G, Goncalves D, Luo Z, Avruch J, Rodnight R, Neary JT. Related Articles Extracellular ATP stimulates an inhibitory pathway towards growth factor-induced cRaf-1 and MEKK activation in astrocyte cultures. J. Neurochem. 77:1001-9, 2001.

6. Avruch J, Khokhlatchev A, Kyrakis JM, Luo Z, Tzivion G, Vavvas D, and Zhang X-F. Ras activation of the Raf kinase: Tyrosine kinase recruitment of the MAP kinase cascade. Recent Prog. Horm. Res. 56: 127-55, 2001.

7. Lin T, Itani S, Dean DJ, Kurowski TG, Luo ZJ, Yaney GC, and Ruderman NB. Inhibition of insulin signaling and glycogen synthesis by phorbol dibutyrate in rat skeletal muscle. Am. J. Physiol. 281: E8-E15, 2001.

8. Zang M, Waelde CA, Xiang X, Rana A, Wen Rong, and Luo Z. Activation of Raf-1 by EGF and disrupting microtubule integrity through different mechanisms. J. Biol. Chem. 276: 25157-25165, 2001.

9. Zang M, Hayne C, and Luo Z. Interaction between active Pak1 and Raf-1 is necessary for phosphorylation and activation of Raf-1. J. Biol. Chem. 277: 4395-4405, 2002.

10. Xiang X, Yuan M, Ruderman N, and Luo Z. 14-3-3 facilitates insulin-stimulated dissociation of IRS-1 from high speed pellet fraction. Mol. End. 16: 552-562, 2002.

11. Xu C. W. and Luo Z. Inactivation of Ras function by allele-specific peptide aptamers. Oncogene 21: 5753-5757, 2002.

12. Xiang X, Zang M, Waelde CA, Wen R, and Luo Z. Phosphorylation of S338SYY341 regulates specific interaction between Raf-1 and MEK1. J. Biol. Chem 277: 44996-45003, 2002.

13. Luo ZG, Wang Q, Zhou JZ, Wang JB, Luo Z, Liu M, He X, Wynshaw-Boris A, Xiong WC, Lu B, and Mei L. Regulation of AchR clustering by Dishevelled interacting with MuSK and Pak1. Neuron. 35: 489-505, 2002.

14. Tomas E, Lin YS, Dagher Z, Saha A, Luo Z, Ido Y, Ruderman NB. Hyperglycemia and insulin resistance: possible mechanisms. Ann N Y Acad Sci 967: 43-51, 2002.


	Zhijun Luo, M.D., Ph.D. Molecular Mechanisms in Insulin Action and Resistance The research interests of my lab focus on insulin action and insulin resistance. An ongoing research project is the elucidation of the mechanism by which Raf is activated by vRas, insulin and growth factors. Our second project is to examine the role of AMPK in regulation of energy homeostasis in adipocytes and explore its relationship with insulin signal transduction. In addition, we are interested in the regulation of glucose, fatty acid and protein metabolisms by AMPK in cancer cells such as prostate cancer cells. References: 1. Kurowski TG, Lin Y, Luo ZJ, Tschlis PN, Buse MG, Heydrick SJ, and Ruderman N. Hyperglycemia inhibits insulin activation of AKT/protein kinase B but not phosphatidylinositol 3-kinase in Raf skeletal muscle. Diabetes 48, 1999. 2. Tzivion G, Luo ZJ, and Avruch, J. Calyculin A induced vimentin phosphorylation sequesters 14-3-3 and displaces other 14-3-3 partners in vivo. J. Biol. Chem. 275: 29772-29778, 2000. 3. Lenz G, Gottfried C, Luo Z, Avruch J, Rodnight R, Nie WJ, Kang Y, and Neary JT. P2Y purinoceptor subtypes recruit different Mek activators in astrocytes. British J. Pharmacology 129: 927-936, 2000. 4. Hayne C, Tzivion G, and Luo Z. Raf-1/MEK/MAPK pathway is necessary for the G2/M transition induced by nocodazole. J. Biol. Chem. 275:31876-31882, 2000. 5. Lenz G, Goncalves D, Luo Z, Avruch J, Rodnight R, Neary JT. Related Articles Extracellular ATP stimulates an inhibitory pathway towards growth factor-induced cRaf-1 and MEKK activation in astrocyte cultures. J. Neurochem. 77:1001-9, 2001. 6. Avruch J, Khokhlatchev A, Kyrakis JM, Luo Z, Tzivion G, Vavvas D, and Zhang X-F. Ras activation of the Raf kinase: Tyrosine kinase recruitment of the MAP kinase cascade. Recent Prog. Horm. Res. 56: 127-55, 2001. 7. Lin T, Itani S, Dean DJ, Kurowski TG, Luo ZJ, Yaney GC, and Ruderman NB. Inhibition of insulin signaling and glycogen synthesis by phorbol dibutyrate in rat skeletal muscle. Am. J. Physiol. 281: E8-E15, 2001. 8. Zang M, Waelde CA, Xiang X, Rana A, Wen Rong, and Luo Z. Activation of Raf-1 by EGF and disrupting microtubule integrity through different mechanisms. J. Biol. Chem. 276: 25157-25165, 2001. 9. Zang M, Hayne C, and Luo Z. Interaction between active Pak1 and Raf-1 is necessary for phosphorylation and activation of Raf-1. J. Biol. Chem. 277: 4395-4405, 2002. 10. Xiang X, Yuan M, Ruderman N, and Luo Z. 14-3-3 facilitates insulin-stimulated dissociation of IRS-1 from high speed pellet fraction. Mol. End. 16: 552-562, 2002. 11. Xu C. W. and Luo Z. Inactivation of Ras function by allele-specific peptide aptamers. Oncogene 21: 5753-5757, 2002. 12. Xiang X, Zang M, Waelde CA, Wen R, and Luo Z. Phosphorylation of S338SYY341 regulates specific interaction between Raf-1 and MEK1. J. Biol. Chem 277: 44996-45003, 2002. 13. Luo ZG, Wang Q, Zhou JZ, Wang JB, Luo Z, Liu M, He X, Wynshaw-Boris A, Xiong WC, Lu B, and Mei L. Regulation of AchR clustering by Dishevelled interacting with MuSK and Pak1. Neuron. 35: 489-505, 2002. 14. Tomas E, Lin YS, Dagher Z, Saha A, Luo Z, Ido Y, Ruderman NB. Hyperglycemia and insulin resistance: possible mechanisms. Ann N Y Acad Sci 967: 43-51, 2002.