The applicant is fully committed to a career in laboratory-based investigation and has designed this proposal to build upon and to broaden the skills and scientific interests developed during his fellowship training. The studies outlined in this proposal will enable the applicant to apply this background to questions that are fundamental to understanding aspects of hormonal signal transduction and regulation of cellular proliferation.
The aim of the proposed project is to investigate the hepatocellular mechanisms of ionic signaling in response to growth factors, specifically to identify growth factor activated ion entry pathways and the mechanisms by which this activation occurs, and also to identify the role of altered ion flux in modulating proto-oncogene expression, an early downstream growth factor response. The experimental design employs several complementary approaches to address the overall goals. These approaches include real-time measurement of growth factor induced perturbations in cytosolic cation concentrations and electrophysiologic detection of ion currents responsible for this perturbation, definition of the role of ionic signaling in modulation of proto-oncogene expression, and expression cloning of growth factor activated ion channels/transporters in Xenopus oocytes.
| Lidofsky, S D; Sostman, A; Fitz, J G (1997) Regulation of cation-selective channels in liver cells. J Membr Biol 157:231-6 |
| Lidofsky, S D (1995) Convergent and parallel activation of low-conductance potassium channels by calcium and cAMP-dependent protein kinase. Proc Natl Acad Sci U S A 92:7115-9 |
| Brown Jr, R S; Lomri, N; De Voss, J et al. (1995) Enhanced secretion of glycocholic acid in a specially adapted cell line is associated with overexpression of apparently novel ATP-binding cassette proteins. Proc Natl Acad Sci U S A 92:5421-5 |
| Lidofsky, S D; Xie, M H; Sostman, A et al. (1993) Vasopressin increases cytosolic sodium concentration in hepatocytes and activates calcium influx through cation-selective channels. J Biol Chem 268:14632-6 |
| Fitz, J G; Lidofsky, S D; Xie, M H et al. (1991) Plasma membrane H(+)-HCO3- transport in rat hepatocytes: a principal role for Na(+)-coupled HCO3- transport. Am J Physiol 261:G803-9 |
