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Vanderbilt-Ingram Cancer CenterVanderbilt-Ingram Cancer Center

Graham F.  Carpenter

Graham F. Carpenter, Ph.D.

Professor of Biochemistry, Emeritus
VICC Member

Contact Information:

Vanderbilt University Medical Center
647 Light Hall
Nashville, TN 37232-0146

Research Specialty

Growth Factor Signal Transduction/Trafficking of Growth Factor Receptors

Research Description

The focus of research in this laboratory is understanding the mechanisms by which growth factors regulate the proliferation of mammalian cells. In particular, we utilize the polypeptide mitogen epidermal growth factor (EGF) and cultures of mammalian cells as a model system. Specific research interests at the present time involve two interrelated aspects of the mechanism of action of EGF. The first area centers on the generation of second messenger molecules or intracellular signals in response to the binding of EGF to its receptor on the surface of target cells. The receptor, a transmembrane protein, contains an intrinsic tyrosine kinase activity in the cytoplasmic domain. Recently, this laboratory identified a particular phospholipase C isozyme (PLC-gamma 1) as an important phosphorylation substrate of the EGF receptor. Also, we have shown that tyrosine phosphorylation of PLC-gamma 1 increases its catalytic activity to generate the second messenger molecules IP3 and diacylglycerol. Various approaches are now being used to understand the biology and biochemistry of this protein. This includes targeted disruption of the PLC-gamma 1 gene in mice, analysis of the biological properties of PLC-gamma 1 null cells derived from such mice, and mutagenesis of the PLC-gamma 1 molecule.

The second focus of research involves receptor tyrosine kinases, known as ErbB receptors, that bind the EGF/heregulin growth factors and mediate cell proliferation/differentiation. In particular, the laboratory is focused on the proteolytic processing as a mechanism for nuclear translocation and signal transduction for the ErbB-4 receptor. Also, a project focused on the trafficking of ErbB-1 to the nucleus without proteolytic processing is underway.