Wn mutation of c-kit receptor affects its post-translational processing and extracellular expression
Koshimizu, U.; Tsujimura, T.; Isozaki, K.; Nomura, S.; Furitsu, T.; Kanakura, Y.; Kitamura, Y.; Nishimune, Y.
Oncogene 9(1): 157-162
1994
ISSN/ISBN: 0950-9232 PMID: 7508100 Document Number: 428278
The W locus of mice encodes the c-kit receptor tyrosine kinase. Recently, we characterized a novel mutant allele, W-n, and demonstrated that the c-kit protein synthesized in W-n/W-n cultured mast cells (CMC) was reduced in size and not expressed on their surface (Tsujimura et al., 1993). In this study, we further examined biochemical nature of the mutant form of c-kit protein, by using W-n/Wn CMC and 293T cells transfected with W-n-type c-kit cDNA (c-kit-Wn). The c-kit product synthesized in W-n/W-n CMC was truncated almost all cytoplasmic domain and was less glycosylated. In c-kit-Wn-transfected cells, both glycosylation and extracellular expression of c-kit protein was also impaired, however, no truncation was detected. These results indicate that W-n-mutant form of c-kit product is insufficient in maturation, which is associated with impairments in the transport to the plasma membrane, and retention of the mutant protein in endoplasmic reticulum is suggested. This is the first demonstration of the c-kit mutation affecting posttranslational processing its product.