Office: 210-567-3097
Email: liuf@uthscsa.edu

Our primary interest lies in studying the insulin signal transduction pathway, which is activated when the hormone insulin binds to its cell surface receptors, resulting in a cascade of biochemical reactions that culminates in regulation of metabolic processes such as glucose uptake and glycogen synthesis. Defects in any of the steps along this signaling cascade can result in insulin resistance, one of the primary contributors to developing Type 2 diabetes. In order to better understand the molecular mechanism of insulin signal transduction and insulin resistance, we are using molecular biology, biochemistry, and cell biology approaches as well as animal models to identify and characterize signaling components involved in insulin receptor signaling processes. It is our hope that better understanding of the signaling components involved in mediating insulin signal transduction will generate information that may be contributed to the development of new therapeutic drugs for the treatment of Type 2 diabetes.

We are also interested in investigating the link between insulin signaling and aging. Recent studies from invertebrates suggested that reducing insulin/IGF-1 signaling in the neurons can extend the life-span of these organisms. Whether reducing neuronal insulin/IGF-1 signaling in mammals extends their life-span remains to be established. We are currently developing animal models in order to determine whether neuronal insulin signaling plays a role in regulating mammalian longevity and aging.

Selected Publications

Wang, L., Balas, B., Christ-Roberts, C.Y., Kim, R.Y., Ramos, F.J., Kikani, C.K., Li, C., Deng, C., Reyna, S., Musi, N., Dong, L.Q., DeFronzo, R.A., and Liu, F. (2007) Perpheral disruption of Grb10 gene enhances insulin signaling and sensitivity in vivo. Mol. Cell. Biol. In press.

Wang C., Mao, X., Wang, L., Liu, M., Wetzel, M.D., Guan, K.-L., Dong, L.Q., and Liu, F. (2007) Adiponectin sensitizes insulin signaling by reducing p70 S6 kinase-mediated serine phosphorylation of IRS-1. J. Biol Chem. 282:7991-7996.

Li, J., Mao, X., Dong, L.Q., Liu, F., Tong, L. (2007) Crystal Structures of the BAR-PH and PTB Domains of Human APPL1. Structure 15:525-533.

Riojas, R.A., Kikani, C.K., Wang, C., Mao, X., Zhou, L., Langlais, P.R., Hu, D., Roberts, J.L., Dong, L.Q., Liu, F. (2006) Fine-tuning PDK1 activity by phosphorylation at Ser163. J. Biol. Chem. 281:21588-21593.

Mao, X., Langlais, P., Riojas, R.J., Wang, L., Ramos, F.J., Fang, Q., Christ-Roberts, C., Hong, J., Kim, R.Y., Kikani, C.K., Liu, F. Dong, L.Q. (2006) APPL1 binds to adiponectin receptors and mediates adiponectin signaling and function. Nat. Cell. Biol. 8:516-523.

Ramos, F.J., Langlais, P., Hu, D., Dong, L.Q., and Liu, F. (2006) Grb 10-mediated degradation of the insulin receptor: A mechanism of negative regulation. Am. J. Physiol. Endocrinol. Metab. E1262-1266.

Dong L.Q., Liu F. (2005) PDK2: The missing piece in the receptor tyrosine kinase signaling pathway puzzle. Am J Physiol Endocrinol Metab 289:E187-196.

Kikani, C.K., Dong, L.Q., and Liu, F. (2005) "New"-clear functions of PDK1: Beyond a master kinase in the cytosol. J Cell. Biochem. 96, 1157-1162.

Langlais P., Wang C., Dong L.Q., Carroll C.A., Weintraub S.T., Liu F. (2005) Phosphorylation of Grb10 by mitogen-activated protein kinase: identification of Ser150 and Ser476 of human Grb 10zeta as major phosphorylation sites. Biochemistry 44:8890-8897.

Lim M., Moon S. Y., Zheng Y., Wu H., Dong L.Q., and Liu F. (2004) Roles of PDK-1 and PKN in regulating cell migration and cortical actin formation of PTEN-deficient cells. Oncogene, 23, 9348-9358.

Langlais P., Dong L.Q., Ramos F.J., Hu D., Li Y., Quon M.J., and Liu F. (2004) Negative Regulation of Insulin-Stimulated MAP Kinase Signaling By Grb10. Mol. Endocrinol. 18, 350-358.

Wick, K.R. Werner, E.D., Langlais, P., Ramos, F.J., Dong, L.Q., Shoelson, S.E., and Liu, F. (2003) Grb10 Inhibits Insulin-stimulated Phosphorylation of IRS-1/IRS-2 and Delays Akt Activation by Disrupting the Association of IRS-1/IRS-2 with the Insulin Receptor. J. Biol. Chem. 278, 8460-8467.

Wick, M.J., Wick, K. R., Dong, L.Q., and Liu, F. (2002) Autophosphorylation at Thr516 and Ser399 is important for the activity and function of 3-Phosphoinositide-dependent protein kinase-1 (PDK1). J. Biol. Chem. 277: 16632-16638.

Wick, M.J., and Dong, L.Q., Hu, D., Langlais, P., and Liu, F (2001) Insulin receptor-mediated p62dok tyrosine phosphorylation at Residues 362 and 398 plays distinct roles for binding GAP and Nck and is essential for inhibiting insulin-stimulated activation of Ras and Akt . J. Biol. Chem., 276, 42843-42850.

Dong, L.Q., Landa, L.R., Wick, M.J., Zhu, L., Mukai, H., Ono, Y. and Liu, F.. Phosphorylation of PKN by PDK1 mediates insulin signals to the actin cytoskeleton. Proc. Natl. Acad. Sci. USA. 97, 5089-5094, 2000.