Defective posttranslational processing activates the tyrosine kinase encoded by the MET proto-oncogene (hepatocyte growth factor receptor).

作者: A Mondino , S Giordano , P M Comoglio

DOI: 10.1128/MCB.11.12.6084

关键词:

摘要: The MET proto-oncogene encodes a 190-kDa disulfide-linked heterodimeric receptor (p190 alpha beta) whose tyrosine kinase activity is triggered by the hepatocyte growth factor. mature made of two subunits: an chain 50 kDa and beta 145 kDa, arising from proteolytic cleavage single-chain precursor 170 (pr170). In colon carcinoma cell line (LoVo), not cleaved Met protein exposed at surface as polypeptide 190 (p190NC). expression uncleaved due to defective posttranslational processing, since in this (i) site Lys-303-Arg-Lys-Lys-Arg-Ser-308 present precursor, (ii) p190NC sensitive mild trypsin digestion surface, generating chains correct size, (iii) 205-kDa insulin well. functional vitro activated vivo, shown constitutive autophosphorylation on tyrosine. gene neither amplified nor rearranged LoVo cells. Overlapping cDNA clones selected library derived mRNA were sequenced. No mutations MET-coding region. These data indicate that encoded can be consequence defect.

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