Stem cell factor 248 (SCF248)

Stem cell factor 248 (SCF248) is the primary cleavable isoform of the cytokine Stem cell factor (SCF), also known as KIT ligand [1, 11]. It is encoded by the KITLG gene and serves as the essential ligand for the c-Kit receptor tyrosine kinase (CD117) [1, 8]. SCF248 contains a unique proteolytic cleavage site encoded by exon 6, which allows its extracellular domain to be shed as a soluble factor, whereas the shorter SCF220 isoform remains largely membrane-bound [7, 11]. This soluble form is significantly upregulated in chronic inflammatory and fibrotic conditions, such as idiopathic pulmonary fibrosis (IPF) and asthma, where it promotes the accumulation and activation of mast cells and pro-fibrotic fibroblasts [1, 2, 6]. Therapeutic strategies targeting SCF248, such as the monoclonal antibody INS1148, aim to selectively neutralize this soluble isoform to inhibit pathogenic remodeling while sparing the homeostatic functions of membrane-bound SCF, such as erythropoiesis and tissue repair [10, 12]. This selective approach provides a mechanism to modulate c-Kit signaling in disease contexts while potentially minimizing systemic toxicities associated with non-selective c-Kit inhibition [12].

Other names

KIT ligandKITLGMast cell growth factorMGFSteel factorSFc-Kit ligandKLHematopoietic growth factorSoluble stem cell factorsSCF

Selective neutralization of the soluble SCF248 isoform to inhibit pathogenic c-Kit-mediated signaling in mast cells and fibroblasts while preserving the homeostatic functions of the membrane-bound SCF isoform.