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

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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

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Ankyrin Repeat
COS Cells
Substrates
Immunoprecipitation
Proteins
Chemical activation
Proto-Oncogene Proteins c-raf
Sf9 Cells
Thymus
T-cells
Terminal Repeat Sequences
Baculoviridae
Protein-Serine-Threonine Kinases
Chromosomes
Nuclear Proteins
Gene Library
Epidermal Growth Factor
Thymus Gland
Fluorescent Antibody Technique
Insects

ASJC Scopus subject areas

  • Biochemistry

Cite this

The ankyrin repeat-containing adaptor protein Tvl-1 is a novel substrate and regulator of Raf-1. / Lin, Jun Hsiang; Makris, Antonios; McMahon, Christine; Bear, Susan E.; Patriotis, Christos; Prasad, Vinayaka R.; Brent, Roger; Golemis, Erica A.; Tsichlis, Philip N.

In: Journal of Biological Chemistry, Vol. 274, No. 21, 21.05.1999, p. 14706-14715.

Research output: Contribution to journalArticle

Lin, JH, Makris, A, McMahon, C, Bear, SE, Patriotis, C, Prasad, VR, Brent, R, Golemis, EA & Tsichlis, PN 1999, 'The ankyrin repeat-containing adaptor protein Tvl-1 is a novel substrate and regulator of Raf-1', Journal of Biological Chemistry, vol. 274, no. 21, pp. 14706-14715. https://doi.org/10.1074/jbc.274.21.14706
Lin, Jun Hsiang ; Makris, Antonios ; McMahon, Christine ; Bear, Susan E. ; Patriotis, Christos ; Prasad, Vinayaka R. ; Brent, Roger ; Golemis, Erica A. ; Tsichlis, Philip N. / The ankyrin repeat-containing adaptor protein Tvl-1 is a novel substrate and regulator of Raf-1. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 21. pp. 14706-14715.
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