PMID- 10329666 OWN - NLM STAT- MEDLINE DCOM- 19990709 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 274 IP - 21 DP - 1999 May 21 TI - The ankyrin repeat-containing adaptor protein Tvl-1 is a novel substrate and regulator of Raf-1. PG - 14706-15 AB - 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. FAU - Lin, J H AU - Lin JH AD - Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. FAU - Makris, A AU - Makris A FAU - McMahon, C AU - McMahon C FAU - Bear, S E AU - Bear SE FAU - Patriotis, C AU - Patriotis C FAU - Prasad, V R AU - Prasad VR FAU - Brent, R AU - Brent R FAU - Golemis, E A AU - Golemis EA FAU - Tsichlis, P N AU - Tsichlis PN LA - eng SI - GENBANK/AF123704 GR - CA06927/CA/NCI NIH HHS/United States GR - R01-CA38147/CA/NCI NIH HHS/United States GR - T32-CA09683/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Carrier Proteins) RN - 0 (DNA-Binding Proteins) RN - 0 (Rfxank protein, mouse) RN - 0 (Transcription Factors) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-raf) SB - IM MH - *Adaptor Proteins, Signal Transducing MH - Amino Acid Sequence MH - Animals MH - *Ankyrin Repeat MH - Carrier Proteins/isolation & purification/*physiology MH - Cells, Cultured MH - DNA-Binding Proteins MH - Molecular Sequence Data MH - Proto-Oncogene Proteins c-raf/*physiology MH - Substrate Specificity MH - Transcription Factors EDAT- 1999/05/18 00:00 MHDA- 1999/05/18 00:01 CRDT- 1999/05/18 00:00 PHST- 1999/05/18 00:00 [pubmed] PHST- 1999/05/18 00:01 [medline] PHST- 1999/05/18 00:00 [entrez] AID - 10.1074/jbc.274.21.14706 [doi] AID - S0021-9258(19)73147-0 [pii] PST - ppublish SO - J Biol Chem. 1999 May 21;274(21):14706-15. doi: 10.1074/jbc.274.21.14706.