Alan R. Saltiel, Ph.D. ~John Jacob Abel Professor in the Life Sciences ~Director of the Life Sciences Institute University of Michigan Phone: (734) 615-9787 Fax:    (734) 936-2888 saltiel@umich.edu Saltiel Lab Homepage

Current Research: 

One area of investigation includes the compartmentalization of signal initiation from receptors in the plasma membrane. We have studied the plasma membrane microdomains called lipid rafts and caveolae. These microdomains serve as organelles for specific signals, providing sites for the segregation of signal transduction. Our studies have lead to the identification of a new pathway in insulin action that relies on the translocation of a signaling unit to this interesting domain. This work included the cloning of a new family of adapter proteins, which also functions in other signaling systems. Current investigations focus on downstream activation of G proteins, protein kinase cascades and changes in the actin cytoskeleton, which involve biochemical and immunocytochemical analyses of protein localization and interactions, evaluation of cellular metabolism, and manipulation of genes through targeted disruption and transgenics in mice.

Another area of investigation concerns the organization of targets of signal transduction in the cell. Insulin promotes the dephosphorylation of many enzymes of intermediary metabolism, via pathways that remain poorly understood. We have cloned two families of “scaffolding” proteins that localize enzymes such as glycogen synthase, protein phosphatase 1 and hormone sensitive lipase to discrete domains in cells, permitting these proteins to receive signals from the insulin receptor. Current studies are focused on understanding the signaling pathways that link the insulin receptor to these compartmentalized changes in phosphorylation. These efforts involve the construction of chimeric proteins, evaluation of protein:protein interactions using both protein purification and genetic screens, and targeted disruption of the important genes in mice, to study the physiological role of these pathways in glucose and lipid metabolism.

One important question that will be investigated concerns the importance of these new pathways in disorders of glucose and lipid metabolism. Type 2 diabetes is associated with insulin resistance, a common disorder in which patients do not respond to normal circulating concentrations of insulin. The precise function of these pathways, and their roles in the pathogenesis of diabetes are under investigation, with the goal of developing new therapeutic approaches to the treatment of diabetes and related disorders.

Selected Publications:

Saltiel, A.R. "You Are What You Secrete" (2001) Nature Medicine 7, 887

Saltiel, A.R. and Kahn, C.R. "Insulin Signaling and the Regulation of Glucose and Lipid Metabolism" (2001) Nature 414, 789

Saltiel, A.R. and Pessin, J.E. "Insulin Signaling Pathways in Time and Space" (2002) Trends in Cell Biology 12, 65

Saltiel, A.R. "Muscle or Fat? Rho Bridges the GAP" (2003) Cell 113, 144

Saltiel, A.R. and Pessin, J.E. "Insulin signaling in microdomains of the plasma membrane" Traffic (2003) 4 , 711

Saltiel, A.R. "Tugging on Glucose Transport" (2003) Nature Medicine 9 , 1352

Saltiel, A.R. " Putting the Breaks on Insulin Signaling" New Eng J Med. (in press)

Articles accepted for publication

Pessin, J.E. and Saltiel, A.R. "Molecular basis for insulin receptor signaling specificity". Biochemical Society Transactions. (in press)

Hou, J.C., Saltiel, A.R. and Pessin, J.E. "Cellular and Molecular Processes Regulating GLUT4 translocation" Diabetes Mellitus ed. J Olefsky (in press)

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