Cynthia Corley Mastick, Associate Professor
B.S. (1985), Ph.D. (1990) Carnegie Mellon University, Pittsburgh, PA.

Research Interests:

Research in the lab focuses on specificity in signal transduction. Our major area of interest is in insulin signaling, insulin resistance, and diabetes. To maintain specificity, signaling proteins are organized into signal transduction modules by scaffolding proteins and by localization in specialized compartments. We study signaling modules in caveolae, which are specialized domains of the plasma membrane defined by their coat proteins, the caveolins. The caveolins are scaffolding proteins that bind to specific signaling molecules and cluster them at the cell surface. Recently we have identified a novel feedback inhibition loop involving Src-family kinases, c-terminal Src kinase (Csk), and caveolin.

In adipocytes, insulin stimulates glucose transport, lipogenesis, and glycogen synthesis ten to hundreds of fold, while other growth factors such as PDGF or EGF do not. The insulin-specific signaling pathways that account for this differential regulation have remained elusive. Identification of these pathways is critical for an understanding of the insulin resistance that underlies type II diabetes. Stimulation of adipocytes with insulin, but not with PDGF or EGF, leads to the rapid phosphorylation of caveolin. Current work focuses on the relationship of this phosphorylation to glucose and lipid metabolism.

Glucose uptake into fat and muscle is controlled via regulated secretion of GluT4, an isoform of glucose transporter. GluT4 is translocated from an intracellular, vesicular pool to the plasma membrane in response to insulin. This process shares protein components with other regulated secretory events including synaptic vesicle exocytosis. Insulin also regulates glycogen and lipid synthesis through the activation of specific pools of type I protein serine phosphatase (PP1). We are currently exploring the mechanism through which insulin regulates GluT4 exocytosis and PP1 activity.

Representative Publications:

Cao H, Sanguinetti AR, Mastick CC. Oxidative stress activates both Src-kinases and their negative regulator Csk and induces phosphorylation of two targeting proteins for Csk: caveolin-1 and paxillin. (2004) Exp Cell Res, 294:159-171.

Sanguinetti AR, Cao H, Mastick CC. Fyn is required for oxidative- and hyperosmotic-stress-induced tyrosine phosphorylation of caveolin-1. (2003) Biochem J, 376:159-168.

Mastick CC, Brady MJ, Saltiel AR. Insulin stimulates the tyrosine phosphorylation of caveolin. (1995) J Cell Biol, 129:1523-1531.

Mastick CC, Aebersold R, Lienhard GE. Characterization of a major protein in GLUT4 vesicles. Concentration in the vesicles and insulin-stimulated translocation to the plasma membrane (1994) J Biol Chem, 269:6089-6092.

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