Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1996-11-15
pubmed:abstractText
The Ron tyrosine kinase receptor shares with the members of its subfamily (Met and Sea) a unique functional feature: the control of cell dissociation, motility, and invasion of extracellular matrices (scattering). The mature Ron protein is a heterodimer of disulfide-linked alpha and beta chains, originated by proteolytic cleavage of a single-chain precursor of 185 kDa. In a human gastric cancer cell line (KATO-III), we found abnormal accumulation of an uncleaved single-chain protein (delta-Ron) of 165 kDa; this molecule is encoded by a transcript differing from the full-length RON mRNA by an in-frame deletion of 49 amino acids in the beta-chain extracellular domain. The deleted transcript originates by an alternatively spliced cassette exon of 147 bp, flanked by two short introns. The delta-Ron tyrosine kinase is constitutively activated by disulfide-linked intracellular oligomerization because it contains an uneven number of cysteine residues. Oligomerization and constitutive tyrosine phosphorylation of the full-size Ron was obtained by site-directed mutagenesis of a single cysteine residue in the region encoded by the cassette exon, mimicking that occurring in the delta-Ron isoform. Inhibition of thiol-mediated intermolecular disulfide bonding prevented delta-Ron oligomerization. The intracellular activation of Ron is followed by acquisition of invasive properties in vitro. These data (i) provide a novel molecular mechanism for posttranscriptional activation of a tyrosine kinase receptor protein and (ii) suggest a role for the Ron receptor in progression toward malignancy.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-1312714, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-1617632, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-1658624, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-1695324, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-1710022, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-1861999, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-2120591, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-2201450, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-2438036, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-2440339, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-2456920, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-2541345, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-2554238, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-2688704, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-2688707, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-271968, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-2819873, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-2837425, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-2849512, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-2871941, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-2891362, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-2927393, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-3037315, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-3304142, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-3455782, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-3525956, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-6320011, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-6590967, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-7592798, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-7623794, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-7822270, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-7824936, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-7935422, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-8062829, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-8127895, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-8144568, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-8205545, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-8289812, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-8302603, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-8386824, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-8388541, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-8392188, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-8641273, http://linkedlifedata.com/resource/pubmed/commentcorrection/8816464-8730094
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0270-7306
pubmed:author
pubmed:issnType
Print
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5518-26
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:8816464-Humans, pubmed-meshheading:8816464-Stomach Neoplasms, pubmed-meshheading:8816464-Genetic Variation, pubmed-meshheading:8816464-Base Sequence, pubmed-meshheading:8816464-Tumor Cells, Cultured, pubmed-meshheading:8816464-Neoplasm Invasiveness, pubmed-meshheading:8816464-Phenotype, pubmed-meshheading:8816464-Enzyme Induction, pubmed-meshheading:8816464-Cell Line, pubmed-meshheading:8816464-Transcription, Genetic, pubmed-meshheading:8816464-Receptors, Cell Surface, pubmed-meshheading:8816464-Recombinant Proteins, pubmed-meshheading:8816464-Exons, pubmed-meshheading:8816464-Introns, pubmed-meshheading:8816464-Receptor Protein-Tyrosine Kinases, pubmed-meshheading:8816464-DNA Primers, pubmed-meshheading:8816464-TATA Box, pubmed-meshheading:8816464-Alternative Splicing, pubmed-meshheading:8816464-Polymerase Chain Reaction
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