Research Interests:

In my lab we are interested in the molecular mechanisms underlying specificity in signal transduction. To ensure signalling specificity, signalling molecules are organized either through the use of scaffolding proteins or by localization in specialized lipid domains in membranes. Caveolae represent one class of specialized lipid ordered domain that is characterized by the presence of the coat proteins termed the caveolins. Caveolins themselves also act as scaffolding proteins, and bind a number of signalling molecules.

We have shown that stimulation of adipocytes with insulin leads to the rapid phosphorylation on tyrosine of two isoforms of caveolin and a 29 kd protein (pp29) that is tightly associated with the caveolins (3-5). This phosphorylation of caveolin is interesting because it shows specificity for insulin, and is not stimulated by PDGF or EGF in these cells. This correlates well with the metabolic effects of insulin in these cells. In adipocytes, glucose transport, lipogenesis, and glycogen synthesis are stimulated ten to hundreds of fold in response to insulin, but these processes show no increase in response to PDGF or EGF. Many other signalling pathways that have been identified for insulin (such as activation of MAP kinase or PI-3-kinase) are shared by all three growth factors. Current work in the lab focuses on the role of the non-receptor tyrosine kinases Fyn and Abl in the stimulation of caveolin phosphorylation by insulin and the role that this phosphorylation plays in cells.

We are also interested in the mechanism by which insulin regulates glucose transport in cells. This process involves a regulated secretory event in which glucose transport proteins are translocated from an intracellular, vesicular pool to the plasma membrane. We have previously shown that this process shares a number of protein components with other regulated secretory events including synaptic vesicle exocytosis (6,7,10). We are currently exploring the role of the synapsin family of phosphoproteins in the regulation of glucose transport by insulin.

Recent Publications:

Caveolae in signalling:

1) Scherer, P.E., M.P. Lisanti, G. Baldini, M. Sargiacomo, C.C. Mastick, and H.F. Lodish (1994) Induction of Caveolin During Adipogenesis and Association of Caveolin with GluT4-rich vesicles. J. Cell Biol., 127, 1233-1243.

2) Wiese, R.J., C.C. Mastick, D.F. Lazar, and A.R. Saltiel (1995) Activation of MAP kinase and Phosphatidylinositol 3'-Kinase is not Sufficient for the Hormonal Stimulation of Glucose Uptake, Lipogenesis, or Glycogen Synthesis in 3T3-L1 Adipocytes. J. Biol. Chem., 270, 3442-3446.

3) Mastick, C.C., M.J. Brady, and A.R. Saltiel (1995) Insulin Stimulates the Tyrosine Phosphorylation of Caveolin. J. Cell Biol., 129, 1523-1531.

4) Mastick, C.C. and A.R. Saltiel (1997) Insulin-Stimulated Tyrosine Phosphorylation of Caveolin is Specific for the Differentiated Adipocyte Phenotype in 3T3-L1 cells. J. Biol. Chem., 272, 20706-20714.

5) Mastick, C.C., M.J. Brady, J.A. Printen, V. Ribon, and A.R. Saltiel (1998) Spatial Determinants of Specificity in Insulin Action. Molecular and Cellular Biochemistry, Focussed Issue on Insulin Action, 182, 65-71.

Regulation of glucose transport:

6) Cain, C.C.*., W.S. Trimble, and G.E. Lienhard (1992) Members of the VAMP Family of Synaptic Vesicle Proteins are Components of Glucose Transporter-containing Vesicles from Rat Adipocytes. J. Biol. Chem., 267, 11681-11684.

7) Laurie, S.M., C.C. Cain*, G.E. Lienhard, and J.D. Castle (1993) The Glucose Transporter GluT4 and Secretory Carrier Membrane Proteins (SCAMPs) Colocalize in Rat Adipocytes and Partially Segregate during Insulin Stimulation. J. Biol. Chem., 268, 19110-19117.

8) Mastick, C.C., R. Aebersold, and G.E. Lienhard (1994) Characterization of a Major Protein in GluT4 Vesicles: Concentration in the Vesicles and Insulin-Stimulated Translocation to the Plasma Membrane. J. Biol. Chem., 269, 6089-6092.

9) Keller, S.R., H.M. Scott, C.C. Mastick, R. Aebersold, and G.E. Lienhard (1995) Cloning and Characterization of a Novel Insulin-regulated Membrane Aminopeptidase from GluT4 Vesicles. J. Biol. Chem., 270, 23612-23618.

10) Mastick, C.C. and A. Falick (1997) Association of NSF, a-SNAP, and g-SNAP with GluT4-Containing Vesicles in Rat Adipocytes. Endocrinology, 138, 2391-2397.

  *C.C. Cain is now C.C. Mastick  

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