Canine SCF (stem cell factor; also known as c-kit ligand) is a type I transmembrane (TM) glycoprotein that plays an important role in a number of fetal and adult developmental processes (1-4). It is synthesized as a 274 amino acid (aa) precursor that contains a 25 aa signal sequence, a 190 aa extracellular region, a 23 aa TM segment and a 36 aa cytoplasmic tail (5). Within the extracellular region there are four potential N-linked glycosylation sites, two intrachain disulfide bonds, and four
alpha -helices. Although the predicted molecular weight is 19 kDa, the native molecule is anywhere from 28-40 kDa in size and reflects both N- and O-linked glycosylation (1). Glycosylation is not necessary for bioactivity (6). The transmembrane form of SCF can be cleaved proteolytically, generating a 165 aa soluble form. Circulating SCF exists as both a monomer and nondisulfide-linked homodimer, with monomer predominating (50% to 75%) (6). Both the soluble and TM forms have bioactivity. Their principal targets may be different, however (7). A second, alternate splice short form of SCF has been identified in other species (1). It is membrane bound but lacks the proteolytic cleavage site found in the long form. Thus, it cannot give rise to a soluble molecule. No such isoform has been reported for canine, but it could be assumed to exist. The ratio of long form to short form varies from tissue to tissue (1). Soluble canine SCF shares 88%, 93%, 86%, 83%, 76%, 76%, 86% and 88% aa sequence identity with porcine, feline, bovine, human, mouse, rat, goat and equine SCF, respectively. Cells known to express SCF include endothelial cells, fibroblasts and keratinocytes (1).