The long term goals of this revised Program Project are to understand the molecular pathways that regulate cell growth and trigger specialized cell functions. Understanding these fundamental signalling pathways will contribute to our knowledge of abnormal signalling pathways operative in cancer cells. The mechanisms that control cell growth, differentiation and specialized cell functions involve the complex interactions of cellular receptors with a variety of hormones and mitogens. In addition these cellular processes are profoundly influenced by the interaction of the cell with components of the extracellular matrix, as well as with molecules present on the surface of neighboring cells. The projects outlined in this Program Project application have a common theme in that each project seeks to define and understand the role of protein phosphorylation, catalyzed by tyrosine and/or serine/threonine kinases, in the regulation of well studied and characterized signal transduction pathways. Michael Weber continues his investigation of the EGF receptor and its interactions with pp60src. T. Parsons proposes to study the role of a recently discovered tyrosine kinase, termed Focal Adhesion Kinase, in cellular signalling. J. Garrison builds on studies carried out during the past project period addressing the effects of v-src on inositol lipid signalling. Garrison proposes to explore in detail the nature of v-src stimulation of the enthothelin receptor pathway, focusing on the interactions among the receptor, the G protein, Gq and PLC beta. T. Bender will study the c-myb protein determining how protein phosphorylation regulates its activity as a transcription factor. Projects by Parsons and Crentz involve studies on the signalling pathways that control secretion events in adrenal chromaffin cells. S. Parsons will continue her studies on the role of pp60src of phosphorylation on annexin function. The Program Project will be supported by two Cores, an Administrative Core and a Scientific Core devoted to production of antibodies, productions and purification of proteins and handling of radioactive materials.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
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University of Virginia
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Walters, Dustin M; Lindberg, James M; Adair, Sara J et al. (2013) Inhibition of the growth of patient-derived pancreatic cancer xenografts with the MEK inhibitor trametinib is augmented by combined treatment with the epidermal growth factor receptor/HER2 inhibitor lapatinib. Neoplasia 15:143-55
Guerrero, Michael S; Parsons, J Thomas; Bouton, Amy H (2012) Cas and NEDD9 Contribute to Tumor Progression through Dynamic Regulation of the Cytoskeleton. Genes Cancer 3:371-81
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Tilghman, Robert W; Parsons, J Thomas (2008) Focal adhesion kinase as a regulator of cell tension in the progression of cancer. Semin Cancer Biol 18:45-52
Vomastek, Tomas; Iwanicki, Marcin P; Burack, W Richard et al. (2008) Extracellular signal-regulated kinase 2 (ERK2) phosphorylation sites and docking domain on the nuclear pore complex protein Tpr cooperatively regulate ERK2-Tpr interaction. Mol Cell Biol 28:6954-66

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