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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 Tsichlis, Philip N.
Lin, Jun-Hsiang
Makris, Antonios
McMahon, Christine
Bear, Susan E.
Patriotis, Christos
Prasad, Vinayaka R.
Brent, Roger
Tsichlis, Philip N.
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Journal article
Date
1999-05-21
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Cancer and Cellular Biology
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http://dx.doi.org/10.1074/jbc.274.21.14706
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 serinethreonine 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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Citation
Lin J-H, Makris AM, McMahon C, Bear SE, Patriotis C, Prasad VR, et al. The Ankyrin Repeat-containing Adaptor Protein Tvl-1 Is a Novel Substrate and Regulator of Raf-1. J Biol Chem. 1999 May 21;274(21):14706-14715. doi:10.1074/jbc.274.21.14706.
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Elsevier
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Journal of Biological Chemistry, Vol. 274, Iss. 21
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