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Lewis C. Cantley, PhD

Professor, Department of Medicine, Harvard Medical School

Chief, Signal Transduction, Beth Israel Deaconess Medical Center

Contact Info

Lewis Cantley
Beth Israel Deaconess Medical Center
330 Brookline Avenue
Boston, MA, 02215
Mailstop: Rm 1024
Phone: 617-667-0947
Fax: 617-667-0957


Ligita Stukuls
Beth Israel Deaconess Medical Center
Phone: 617-735-2632

Research Abstract

The major research objective of this laboratory is to understand the biochemical pathways that regulate normal mammalian cell growth and the defects that cause cell transformation. More than 10 years ago this laboratory discovered a phosphoinositide kinase that was activated by growth factor receptors and by oncoproteins. Further characterization of this enzyme revealed that it catalyzed an unexpected reaction, the phosphorylation of phosphatidylinositol at the D-3 position of the inositol ring (Whitman et al., 1988), thus leading to the discovery of a new signal transduction pathway. Subsequent research from this laboratory and other
laboratories showed that PI 3-kinase activation is critical for oncogene-mediated cell transformation, as well as for insulin-dependent stimulation of glucose uptake and metabolism. Recent work from this laboratory and other laboratories revealed that one of the products of PI 3-kinase directly activates the AKT/PKB protein kinase to provide a cell survival signal (Franke et al., 1997). A variety of proteins have evolved
domains that specifically interact with lipid products of the PI 3-kinase as a mechanism of regulated recruitment to cell membranes. The roles of these proteins in cell growth, cell migration and cell survival are under investigation. In addition, this laboratory has knocked out genes for subunits of PI 3-kinase in the mouse in order to better understand the importance of this enzyme in development, immunity and cancers. Another major focus of this laboratory is the structural basis for specificity in protein/protein interactions in signal transduction cascades. In particular, this laboratory has focused on the mechanism by which protein phosphorylation can control the assembly of signaling complexes. A novel oriented peptide library technique was developed to determine optimal phosphopeptides for binding to various protein domains (Songyang et al., 1993). This technique was subsequently modified to determine optimal substrates for protein kinases (Songyang et al., 1994,
1995, 1996). Through collaborations with other laboratories it has been possible to determine structures of protein-peptide complexes and thus explain how specificity in signaling is maintained (Yaffe et al., 1997a.b). These studies have also allowed predictions of intracellular targets of signaling proteins on the basis of primary sequence data banks.


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