Carcinogenesis, Vol. 21, No. 8, 1507-1512,
August 2000
© 2000 Oxford University Press
Cancer Biology |
Identification of a novel splicing product of the RON receptor tyrosine kinase in human colorectal carcinoma cells
Department of Medicine, University of Colorado School of Medicine and Denver Health Medical Center, 777 Bannock Street, Denver, CO 80204, USA
The RON receptor tyrosine kinase is a 180 kDa heterodimeric protein composed of a 40 kDa 
chain and a 145 kDa ß 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 chain and a short form of the ß 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 ß 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.
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