Kim-1 is a type 1 transmembrane protein with an extracellular Ig domain that undergoes strong induction in the S3 segment of renal epithelial cells after renal injury. Although the function of Kim-1 in the kidney is unknown, Kim-1 is an important asthma susceptibility gene. It is proposed to be the cellular receptor for the hepatitis A virus and Kim-1 expression is upregulated in almost all renal cell carcinomas. We hypothesize that Kim-1 regulates renal epithelial cell adhesion and migration. After renal epithelial injury, induction of Kim-1 may serve to tether injured but viable cells to the basement membrane, preventing sloughing and intratubular cast formation. In the proposed studies we will characterize the intracellular localization of Kim-1 and investigate colocalization with focal adhesions. We will determine whether ectodomain shedding is necessary for Kim-1 dependent adhesion and migration. The downstream signaling pathways activated by Kim-1 will be investigated using the yeast two-hybrid approach and ligand-affinity chromatography. The proposed studies will have great relevance in understanding the molecular mechanisms of renal regeneration and renal cell cancer invasion and metastasis.
| Humphreys, Benjamin D; Soiffer, Robert J; Magee, Colm C (2005) Renal failure associated with cancer and its treatment: an update. J Am Soc Nephrol 16:151-61 |
| Humphreys, Benjamin D; Forman, John P; Zandi-Nejad, Kambiz et al. (2005) Acetaminophen-induced anion gap metabolic acidosis and 5-oxoprolinuria (pyroglutamic aciduria) acquired in hospital. Am J Kidney Dis 46:143-6 |
