Wn mutation of c-kit receptor affects its post-translational processing and extracellular expression.
The W locus of mice encodes the c-kit receptor tyrosine kinase. Recently, we characterized a novel mutant allele, Wn, and demonstrated that the c-kit protein synthesized in Wn/Wn 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 Wn/Wn CMC and 293T cells transfected with Wn-type c-kit cDNA (c-kitWn). The c-kit product synthesized in Wn/Wn CMC was truncated almost all cytoplasmic domain and was less glycosylated. In c-kitWn-transected cells, both glycosylation and extracellular expression of c-kit protein was also impaired, however, no truncation was detected. These results indicate that Wn-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.
Koshimizu
U
U
Research Institute for Microbial Diseases, Osaka University, Japan.
Tsujimura
T
T
Isozaki
K
K
Nomura
S
S
Furitsu
T
T
Kanakura
Y
Y
Kitamura
Y
Y
Nishimune
Y
Y
D000483:Alleles; D000818:Animals; D002478:Cells, Cultured; D008407:Mast Cells / Q000737:chemistry; D051379:Mice; D017354:Point Mutation; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016184:Receptors, Colony-Stimulating Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D011518:Proto-Oncogene Proteins; D016184:Receptors, Colony-Stimulating Factor; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases