PMID- 10557308
OWN - NLM
STAT- MEDLINE
DCOM- 19991213
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 23
DP  - 1999 Nov 9
TI  - Functional analysis of CNK in RAS signaling.
PG  - 13259-63
AB  - Connector enhancer of KSR (CNK) is a multidomain protein required for RAS
      signaling. Its C-terminal portion (CNK(C-term)) directly binds to RAF. Herein, we
      show that the N-terminal portion of CNK (CNK(N-term)) strongly cooperates with
      RAS, whereas CNK(C-term) efficiently blocks RAS- and RAF-dependent signaling when
      overexpressed in the Drosophila eye. Two effector loop mutants of RAS(V12), S35
      and C40, which selectively activate the mitogen-activated protein kinase (MAPK)
      and phosphatidylinositol-3-kinase pathways, respectively, do not cooperate with
      CNK. However, a strong cooperation is observed between CNK and RAS(V12G37), an
      effector loop mutant known in mammals to activate specifically the RAL pathway.
      We have identified two domains in CNK(N-term) that are critical for cooperation
      with RAS. Our results suggest that CNK functions in more than one pathway
      downstream of RAS. CNK(c-term) seems to regulate RAF, a component of the MAPK
      pathway, whereas CNK(N-term) seems to be involved in a MAPK-independent pathway.
FAU - Therrien, M
AU  - Therrien M
AD  - Howard Hughes Medical Institute, Department of Molecular and Cell Biology,
      University of California, Berkeley, CA 94720-3200, USA.
FAU - Wong, A M
AU  - Wong AM
FAU - Kwan, E
AU  - Kwan E
FAU - Rubin, G M
AU  - Rubin GM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (CNK protein, Drosophila)
RN  - 0 (Carrier Proteins)
RN  - 0 (Drosophila Proteins)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Carrier Proteins/genetics/*physiology
MH  - Cell Line
MH  - Drosophila
MH  - *Drosophila Proteins
MH  - Eye/enzymology/metabolism/ultrastructure
MH  - MAP Kinase Signaling System/*physiology
MH  - Microscopy, Electron, Scanning
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Mutation
MH  - Transfection
MH  - ras Proteins/*metabolism
PMC - PMC23935
EDAT- 1999/11/11 00:00
MHDA- 1999/11/11 00:01
CRDT- 1999/11/11 00:00
PHST- 1999/11/11 00:00 [pubmed]
PHST- 1999/11/11 00:01 [medline]
PHST- 1999/11/11 00:00 [entrez]
AID - 10.1073/pnas.96.23.13259 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13259-63. doi:
      10.1073/pnas.96.23.13259.