| |
We recently reported the
isolation and partial characterization of a novel membrane-associated protein
designated MAP17. In normal tissues, MAP17 was expressed only in the apical
brush border of proximal tubular epithelial cells of the human adult kidney.
However, MAP17 was diffusely expressed in most carcinomas originating in
the kidney, colon, lung, and breast. Transfection of MAP17 into the HT29
carcinoma cell line markedly decreased cell proliferation in vitro and tumor
growth in vivo, suggesting that MAP17 plays a role, either direct or indirect,
in the control of cell proliferation. In an attempt to elucidate the function
of MAP17, we screened a human kidney cDNA library for interacting proteins
using the yeast two-hybrid system and isolated a novel protein containing
PDZ protein interaction domains, which we have named PDZK1. PDZK1 is a 519-amino
acid protein with a molecular weight of 63 kd; it is expressed in the kidney,
pancreas, liver, gastrointestinal tract, and adrenal cortex. In situ hybridization
experiments showed that the expression of PDZK1 was limited to epithelial
cells. In the kidney, it colocalized with MAP17 in the brush border of proximal
tubular epithelial cells. In addition, PDZK1 was overexpressed in selected
tumors of epithelial origin. Although the function of PDZK1 has yet to be
determined, proteins containing PDZ domains have been shown to play important
roles as diverse as cell-cell interaction, cell differentiation, growth
control, ion channels organization, and signal transduction. This is of
particular interest because MAP17 is localized in areas either of cell-cell
contact or where ion channels are localized, for example in the kidney.
PDZK1 may represent the link between the cell membrane--where it interacts
with MAP17--and other cytoplasmic proteins involved in biologic functions
such as cell proliferation, differentiation, and ion transport. |
