Journal Article

Identification of a novel splicing product of the RON receptor tyrosine kinase in human colorectal carcinoma cells

Ming-Hai Wang, Avrom L. Kurtz and Y.-Q. Chen

in Carcinogenesis

Volume 21, issue 8, pages 1507-1512
Published in print August 2000 | ISSN: 0143-3334
Published online August 2000 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/21.8.1507
Identification of a novel splicing product of the RON receptor tyrosine kinase in human colorectal carcinoma cells

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The RON receptor tyrosine kinase is a 180 kDa heterodimeric protein composed of a 40 kDa α chain and a 145 kDa β chain with intrinsic tyrosine kinase activity. Activation of RON causes cell dissociation, motility and invasion of extracellular matrices, suggesting that RON might be involved in tumor metastasis. We report here the cloning of a novel splice variant of RON in human colorectal carcinoma cell line HT-29. This RON variant is first produced as a single chain precursor with a molecular mass of 160 kDa. Proteolytic cleavage results in a 40 kDa α chain and a short form of the β chain with a molecular mass of 125 kDa. The altered receptor is synthesized from a transcript differing from the full-length RON mRNA by an in-frame deletion of 109 amino acids in the extracellular domain of the RON β chain. The consequence of the deletion is constitutive activation of the protein with autophosphorylation. Expression of the RON variant in colon epithelial CoTr cells results in increased cell migration and invasion of extracellular matrices. These data suggest that generation of the activated splice variant of RON may contribute to the invasive phenotype of human colorectal carcinomas in vivo.

Keywords: DMEM, Dulbecco's modified Eagle's medium; ECL, enhanced chemiluminescence; MSP, macrophage stimulating protein; RT, reverse transcription.

Journal Article.  5189 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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