The ankyrin repeat-containing adaptor protein Tvl-1 is a novel substrate and regulator of Raf-1

Jun Hsiang Lin, Antonios Makris, Christine McMahon, Susan E. Bear, Christos Patriotis, Vinayaka R. Prasad, Roger Brent, Erica A. Golemis, Philip N. Tsichlis

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Tvl-1 is a 269-amino acid ankyrin repeat protein expressed primarily in thymus, lung, and testes that was identified by screening a murine T-cell two-hybrid cDNA library for proteins that associate with the serine-threonine kinase Raf-1. The interaction of Tvl-1 with Raf-1 was confirmed by co- immunoprecipitation of the two proteins from COS-1 cells transiently transfected with Tvl-1 and Raf-1 expression constructs as well as by co- immunoprecipitation of the endogenous proteins from CV-1 and NB2 cells. Tvl- 1 interacts with Raf-1 via its carboxyl-terminal ankyrin repeat domain. The same domain also mediates Tvl-1 homodimerization. Tvl-1 was detected by immunofluorescence in both the cytoplasm and the nucleus suggesting that in addition to Raf-1 it may also interact with nuclear proteins. Activated Raf- 1 phosphorylates Tvl-1 both in vitro and in vivo. In baculovirus-infected Sf9 insect cells, Tvl-1 potentiates the activation of Raf-1 by Src and Ras while in COS-1 cells it potentiates the activation of Raf-1 by EGF. These data suggest that Tvl-1 is both a target as well as a regulator of Raf-1. The human homologue of Tvl-1 maps to chromosome 19p12, upstream of MEF2B with the two genes in a head to head arrangement.

Original languageEnglish (US)
Pages (from-to)14706-14715
Number of pages10
JournalJournal of Biological Chemistry
Volume274
Issue number21
DOIs
StatePublished - May 21 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Lin, J. H., Makris, A., McMahon, C., Bear, S. E., Patriotis, C., Prasad, V. R., Brent, R., Golemis, E. A., & Tsichlis, P. N. (1999). The ankyrin repeat-containing adaptor protein Tvl-1 is a novel substrate and regulator of Raf-1. Journal of Biological Chemistry, 274(21), 14706-14715. https://doi.org/10.1074/jbc.274.21.14706