The Novel Murine Ca2+-binding Protein, Scarf, Is Differentially Expressed during Epidermal Differentiation

Abstract

Calcium (Ca2+) signaling-dependent systems, such as the epidermal differentiation process, must effectively respond to variations in (Ca2+) concentration. Members of the Ca2+-binding proteins play a central function in the transduction of (Ca2+) signals, exerting their roles through a (Ca2+) interaction with their target proteins, spatially and temporally. By performing a suppression subtractive hybridization screen we identified a novel mouse gene, Scarf (skin calmodulin-related factor), which has homology to calmodulin (CaM)-like Ca 2+-binding protein genes and is exclusively expressed in differentiating keratinocytes in the epidermis. The Scarf open reading frame encodes a 148-amino acid protein that contains four conserved EF-hand motifs (predicted to be (Ca2+)-binding domains) and has homology to mouse CaM, human CaM-like protein, hClp, and human CaM-like skin protein, hClsp. The functionality of Scarf EF-hand domains was assayed with a radioactive Ca 2+-binding method. By Southern blot and computational genome sequence analysis, a highly related gene, Scarf2, was found 15 kb downstream of Scarf on mouse chromosome 13. The functional Scarf (Ca2+)-binding domains suggest a role in the regulation of epidermal differentiation through the control of(Ca2+)-mediated signaling.