IDENTIFICATION AND PARTIAL CHARACTERIZATION OF PDZK1 - A NOVEL PROTEIN CONTAINING PDZ INTERACTION DOMAINS

We recently reported the isolation and partial characterization of a n ovel membrane-associated protein designated MAP17. In normal tissues, MAP17 was expressed only in the apical brush border of proximal tubula r epithelial cells of the human adult kidney. However, MAP17 was diffu sely expressed in most carcinomas originating in the kidney, colon, lu ng, and breast. Transfection of MAP17 into the HT29 carcinoma cell lin e markedly decreased cell proliferation in vitro and tumor growth in v ivo, suggesting that MAP17 plays a role, either direct or indirect, in the control of cell proliferation. In an attempt to elucidate the fun ction of MAP17, we screened a human kidney cDNA library for interactin g proteins using the yeast two-hybrid system and isolated a novel prot ein containing PDZ protein interaction domains, which we have named PD ZK1. PDZK1 is a 519-amino acid protein with a molecular weight of 63 k d; it is expressed in the kidney, pancreas, liver, gastrointestinal tr act, and adrenal cortex. In situ hybridization experiments showed that the expression of PDZK1 was limited to epithelial cells. In the kidne y, it colocalized with MAP17 in the brush border of proximal tubular e pithelial cells. In addition, PDZK1 was overexpressed in selected tumo rs of epithelial origin. Although the function of PDZK1 has yet to be determined, proteins containing PDZ domains have been shown to play im portant roles as diverse as cell-cell interaction, cell differentiatio n, growth control, ion channels organization, and signal transduction. This is of particular interest because MAP17 is localized in areas ei ther of cell-cell contact or where ion channels are localized, for exa mple in the kidney. PDZK1 may represent the link between the cell memb rane-where it interacts with MAP17- and other cytoplasmic proteins inv olved in biologic functions such as cell proliferation, differentiatio n, and ion transport.