Only the substitution of methionine 918 with a threonine and not with other residues activates RET transforming potential

Anna Maria Cirafici, Giuliana Salvatore, Gabriella De Vita, Francesca Carlomagno, Nina A. Dathan, Roberta Visconti, Rosa Marina Melillo, Alfredo Fusco, Massimo Santoro

Research output: Contribution to journalArticlepeer-review

Abstract

Specific point-mutations of the RET receptor tyrosine kinase protooncogene are responsible for the inheritance of multiple endocrine neoplasia type 2A (MEN2A) and 2B (MEN2B), and familial medullary thyroid carcinoma (FMTC). MEN2B is caused by the substitution of methionine 918 by a threonine in the tyrosine kinase (TK) domain of RET. This mutation converts RET into a dominant transforming oncogene. We have substituted Met918 with four different residues and found that RET acquired transforming activity only when Met918 was substituted with a threonine. However, also when serine and valine, but not leucine or phenylalanine, were inserted in position 918, the RET TK function was activated and induced, especially in the case of the RET(918Ser), immediate-early response genes. We conclude that the preservation of Met918 is critical for the control of RET kinase. However, only when a threonine residue is present in position 918, does RET efficiently couple with a transforming pathway.

Original languageEnglish
Pages (from-to)1450-1455
Number of pages6
JournalEndocrinology
Volume138
Issue number4
DOIs
Publication statusPublished - 1997

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Fingerprint Dive into the research topics of 'Only the substitution of methionine 918 with a threonine and not with other residues activates RET transforming potential'. Together they form a unique fingerprint.

Cite this