PMID- 10064593
OWN - NLM
STAT- MEDLINE
DCOM- 19990429
LR  - 20181113
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 18
IP  - 5
DP  - 1999 Mar 1
TI  - Activation of the Raf/MAP kinase cascade by the Ras-related protein TC21 is
      required for the TC21-mediated transformation of NIH 3T3 cells.
PG  - 1270-9
AB  - TC21 is a member of the Ras superfamily of small GTP-binding proteins and, like
      Ras, has been implicated in the regulation of growth-stimulating pathways. Point 
      mutations introduced into TC21 based on equivalent H-Ras oncogenic mutations are 
      transforming in cultured cells, and oncogenic mutations in TC21 have been
      isolated from several human tumours. The mechanism of TC21 signalling in
      transformation is poorly understood. While activation of the serine/threonine
      kinases Raf-1 and B-Raf has been implicated in signalling pathways leading to
      transformation by H-Ras, it has been argued that TC21 does not activate Raf-1 or 
      B-Raf. Since the Raf-signalling pathway is important in transformation by other
      Ras proteins, we assessed whether the Raf pathway is important to transformation 
      by TC21. Raf-1 and B-Raf are constitutively active in TC21-transformed cells and 
      the ERK/MAPK cascade is required for the maintenance of the transformed state. We
      demonstrate that oncogenic V23 TC21, like Ras, interacts with Raf-1 and B-Raf
      (but not with A-Raf), resulting in the translocation of the Raf proteins to the
      plasma membrane and in their activation. Furthermore, using point mutations in
      the effector loop of TC21, we show that the interaction of TC21 with Raf-1 is
      crucial for transformation.
FAU - Rosario, M
AU  - Rosario M
AD  - CRC Centre for Cell and Molecular Biology, Chester Beatty Laboratories, Institute
      of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
FAU - Paterson, H F
AU  - Paterson HF
FAU - Marshall, C J
AU  - Marshall CJ
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Membrane Proteins)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-raf)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 3.6.1 (Rras2 protein, mouse)
RN  - EC 3.6.5.2 (Monomeric GTP-Binding Proteins)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Cell Membrane/metabolism
MH  - Membrane Proteins/genetics/*metabolism
MH  - Mice
MH  - *Monomeric GTP-Binding Proteins
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-raf/*metabolism
MH  - Signal Transduction
MH  - Transformation, Genetic
MH  - ras Proteins/metabolism
PMC - PMC1171217
EDAT- 1999/03/04 00:00
MHDA- 1999/03/04 00:01
CRDT- 1999/03/04 00:00
PHST- 1999/03/04 00:00 [pubmed]
PHST- 1999/03/04 00:01 [medline]
PHST- 1999/03/04 00:00 [entrez]
AID - 10.1093/emboj/18.5.1270 [doi]
PST - ppublish
SO  - EMBO J. 1999 Mar 1;18(5):1270-9. doi: 10.1093/emboj/18.5.1270.