Nucleotide Sequence of Kidney Androgen-Regulated Protein mRNA and Its Cell-Specific Expression in Tfm/Y Mice

Abstract

Kidney androgen-regulated protein (KAP) mRNA is an abundant renal mRNA that was originally identified by comparisons of the products of in vitro translation of poly(A) RNA from animals before and after androgen stimulation. KAP mRNA is 607 nucleotides long, excluding its poly(A) segment, and encodes a protein of 13,265 mol wt. A hydrophobic N-terminal domain forms a putative signal peptide of 18 amino acids, the cleavage of which results in a 103-amino acid mature protein with a molecular size of 11,297. The protein is highly negatively charged and contains regions of clustered Pro, Glu/Asp, Ser, and Thr residues that are associated with proteins with short half-lives. KAP mRNA is unusual in that it is expressed in two distinct regions of the kidney under different hormonal treatments. It is expressed throughout the cortex in the epithelial lining of the proximal tubules in response to androgen stimulation. After castration, only tubules in the outer stripe of the medulla express KAP mRNA. The androgen receptor-deficient Tfm/Y mutant strain exhibits KAP mRNA induction only in this juxtamedullary region after testosterone treatment. Expression of KAP mRNA in these cells is responsible for the relatively high basal levels of KAP mRNA in female and castrated male animals, and induction in these cells occurs by an androgen receptor (AR)-independent mechanism.