Figure 1
Identification and cloning of RON mRNA transcripts with alterations in the first IPT domain in cancer cell lines. A) Partial sequences of amplified RON cDNA fragments. The sequences show a deletion of 327 nucleotides coded by exons 5 and 6 and an insertion of 60 nucleotides between exons 5 and 6. The deleted sequences that encode 109 amino acids by exons 5 and 6 are italicized (as detected in RON160 cDNA). The inserted sequences encoding 20 new amino acids are underlined (as detected in RONE5/6in cDNA). The beginning and ending of the first IPT unit are indicated. The first nucleotides of exons 5, 6, and 7 are marked with an arrow. The amino acids that act as the digestive site for trypsin-like serine proteases, which led to generation of RONp110, are shown in bold. B) Schematic representation of wild-type RON, RON160, RONE5/6in, and RONp110. Mature RON contains a sema domain (localized in both α and β-chains) followed by a PSI motif and four IPT units. The deletion of exons 5 and 6 and the insertion between exons 5 and 6 in the first IPT unit are indicated with arrows. Cleavage by trypsin-like serine protease in the digestive site results in a truncated variant known as RONp110. Two tyrosine residues (Y1353 and Y1360) in the C-terminal tail are indicated. TM: transmembrane domain; TK: tyrosine kinase domain.