My most recent research experience with Dr. Kilberg, the sponsor of this project proposal, led to the focusing of my efforts on the study of the cellular responses to nutrient deprivation. We have identified an integral plasma membrane protein for which biosynthesis is induced in response to amino acid starvation. The protein is present in the plasma membrane of cultured Fao hepatoma cells and has a molecular weight of 45 kD and an isoelectric point of 5.2 (HPM-45). The function of this protein is unknown and no identical protein has ever been reported as a stress protein. I propose to examine the biosynthesis and regulation of HPM-45 through preparation of mono-specific, polyclonal antibodies and subsequent analysis of the biogenesis of HPM-45 at transcriptional and translational levels. The specificity of HPM-45 induction following amino acid deprivation and the time course of its biosynthesis will be characterized. Specific antibodies to HPM-45 will also allow for the screening of a lambda gtll rat liver expression library. Once identified, a cDNA insert corresponding to the HPM-45 gene will be sub-cloned for use as a molecular probe for mRNA analysis. The detection and characterization of genetic control of HPM-45 by amino acid deprivation will add valuable insight into the cellular response to starvation and the nutritional regulation of gene expression.
| Mailliard, M E; Cariappa, R; Banks, R K (1994) Impairment of glucagon-induced hepatic system A activity by short-term ethanol administration in the rat. Gastroenterology 106:480-7 |
| Fowler, F C; Banks, R K; Mailliard, M E (1992) Characterization of sodium-dependent amino acid transport activity during liver regeneration. Hepatology 16:1187-94 |
| Mailliard, M E; Kilberg, M S (1990) Sodium-dependent neutral amino acid transport by human liver plasma membrane vesicles. J Biol Chem 265:14321-6 |
