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Lin JH , Makris A , McMahon C , Bear SE , Patriotis C , Prasad VR , Brent R , Golemis EA , Tsichlis PN
The ankyrin repeat-containing adaptor protein Tvl-1 is a novel substrate and regulator of Raf-1
Journal of Biological Chemistry. 1999 May 21;274(21) :14706-14715
PMID: ISI:000081965200031   
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Abstract
Tvl-1 is a 269-amino acid ankyrin repeat protein ex pressed 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.
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Times Cited: 16 English Article 225MK J BIOL CHEM