Identification of a novel type of alternative splicing of a tyrosine kinase receptor. Juxtamembrane deletion of the c-met protein kinase C serine phosphorylation regulatory site.

作者: K. M. Yamada , Chong-Chou Lee

DOI: 10.1016/S0021-9258(17)32190-7

关键词:

摘要: We have detected a novel type of structural variant the tyrosine kinase receptor for c-met, also known as hepatocyte growth factor receptor, in mouse tissues. The cDNA transcript c-met lacks 141 base pairs, which predicts an in-frame deletion 47 amino acids juxtamembrane region cytoplasmic domain. Sequence analysis genomic DNA containing locus revealed that absence discrete exon is responsible this 141-base pair and alternative splicing leads to production two forms transcript. These are designated c-metsm (for small) c-metlg large) distinguish or presence segment, respectively. present adult tissues including kidney, liver, brain well 9-10-day-old embryos. In all cases, expression was lower than normal transcript, c-metlg. An antiserum against c-Met protein immunoprecipitated corresponding approximately 152 145 kDa from whole kidney lysate under reducing conditions. size difference 7 between these isoforms corresponds predicted acids. shorter its isoform variety suggests physiological role. deleted domain contains sequence motif (S985ARS) C phosphorylation has recently been shown play key role down-regulation activity. identification isoform, c-metsm, demonstrates can achieve additional diversity by at regulatory site

参考文章(18)
Paolo Comoglio, Silvia Giordano, Maria Flavia Di Renzo, C Rosa, Cs Cooper, Rp Narsimhan, Biosynthesis of the protein encoded by the c-met proto-oncogene. Oncogene. ,vol. 4, pp. 1383- 1388 ,(1989)
L. Mosthaf, K. Grako, T. J. Dull, L. Coussens, A. Ullrich, D. A. McClain, Functionally distinct insulin receptors generated by tissue-specific alternative splicing The EMBO Journal. ,vol. 9, pp. 2409- 2413 ,(1990) , 10.1002/J.1460-2075.1990.TB07416.X
T. Crepaldi, M. Prat, S. Giordano, E. Medico, P.M. Comoglio, Generation of a truncated hepatocyte growth factor receptor in the endoplasmic reticulum. Journal of Biological Chemistry. ,vol. 269, pp. 1750- 1755 ,(1994) , 10.1016/S0021-9258(17)42091-6
M Prat, T Crepaldi, L Gandino, S Giordano, P Longati, P Comoglio, C-terminal truncated forms of Met, the hepatocyte growth factor receptor. Molecular and Cellular Biology. ,vol. 11, pp. 5954- 5962 ,(1991) , 10.1128/MCB.11.12.5954
L. Gandino, P. Longati, E. Medico, M. Prat, P.M. Comoglio, Phosphorylation of serine 985 negatively regulates the hepatocyte growth factor receptor kinase. Journal of Biological Chemistry. ,vol. 269, pp. 1815- 1820 ,(1994) , 10.1016/S0021-9258(17)42099-0
G A Rodrigues, M A Naujokas, M Park, Alternative splicing generates isoforms of the met receptor tyrosine kinase which undergo differential processing. Molecular and Cellular Biology. ,vol. 11, pp. 2962- 2970 ,(1991) , 10.1128/MCB.11.6.2962
M. Park, M. Dean, K. Kaul, M. J. Braun, M. A. Gonda, G. Vande Woude, Sequence of MET protooncogene cDNA has features characteristic of the tyrosine kinase family of growth-factor receptors Proceedings of the National Academy of Sciences of the United States of America. ,vol. 84, pp. 6379- 6383 ,(1987) , 10.1073/PNAS.84.18.6379
F Bussolino, M F Di Renzo, M Ziche, E Bocchietto, M Olivero, L Naldini, G Gaudino, L Tamagnone, A Coffer, P M Comoglio, Hepatocyte growth factor is a potent angiogenic factor which stimulates endothelial cell motility and growth Journal of Cell Biology. ,vol. 119, pp. 629- 641 ,(1992) , 10.1083/JCB.119.3.629
D. Bottaro, J. Rubin, D. Faletto, A. Chan, T. Kmiecik, G. Vande Woude, S. Aaronson, Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product Science. ,vol. 251, pp. 802- 804 ,(1991) , 10.1126/SCIENCE.1846706