PMID- 23250398
OWN - NLM
STAT- MEDLINE
DCOM- 20130524
LR  - 20211021
IS  - 1937-9145 (Electronic)
IS  - 1945-0877 (Linking)
VI  - 5
IP  - 255
DP  - 2012 Dec 18
TI  - A CC-SAM, for coiled coil-sterile alpha motif, domain targets the scaffold KSR-1 to 
      specific sites in the plasma membrane.
PG  - ra94
LID - 10.1126/scisignal.2003289 [doi]
AB  - Kinase suppressor of Ras-1 (KSR-1) is an essential scaffolding protein that 
      coordinates the assembly of the mitogen-activated protein kinase (MAPK) module, 
      consisting of the MAPK kinase kinase Raf, the MAPK kinase MEK (mitogen-activated 
      or extracellular signal-regulated protein kinase kinase), and the MAPK ERK 
      (extracellular signal-regulated kinase) to facilitate activation of MEK and thus 
      ERK. Although KSR-1 is targeted to the cell membrane in part by its atypical C1 
      domain, which binds to phospholipids, other domains may be involved. We 
      identified another domain in KSR-1 that we termed CC-SAM, which is composed of a 
      coiled coil (CC) and a sterile alpha motif (SAM). The CC-SAM domain targeted KSR-1 to 
      specific signaling sites at the plasma membrane in growth factor-treated cells, 
      and it bound directly to various micelles and bicelles in vitro, indicating that 
      the CC-SAM functioned as a membrane-binding module. By combining nuclear magnetic 
      resonance spectroscopy and experiments in cultured cells, we found that membrane 
      binding was mediated by helix alpha3 of the CC motif and that mutating residues in alpha3 
      abolished targeting of KSR-1 to the plasma membrane. Thus, in addition to the 
      atypical C1 domain, the CC-SAM domain is required to target KSR-1 to the plasma 
      membrane.
FAU - Koveal, Dorothy
AU  - Koveal D
AD  - Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, 
      Providence, RI 02903, USA.
FAU - Schuh-Nuhfer, Natasha
AU  - Schuh-Nuhfer N
FAU - Ritt, Daniel
AU  - Ritt D
FAU - Page, Rebecca
AU  - Page R
FAU - Morrison, Deborah K
AU  - Morrison DK
FAU - Peti, Wolfgang
AU  - Peti W
LA  - eng
SI  - PDB/2LPE
GR  - T32 GM007601/GM/NIGMS NIH HHS/United States
GR  - R01 NS056128/NS/NINDS NIH HHS/United States
GR  - S10 RR017269/RR/NCRR NIH HHS/United States
GR  - S10-RR017269/RR/NCRR NIH HHS/United States
GR  - R01NS056128/NS/NINDS NIH HHS/United States
GR  - R01 GM098482/GM/NIGMS NIH HHS/United States
GR  - R01GM098482/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20121218
PL  - United States
TA  - Sci Signal
JT  - Science signaling
JID - 101465400
RN  - 0 (Phospholipids)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.- (KSR-1 protein kinase)
RN  - EC 2.7.11.1 (raf Kinases)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Amino Acid Motifs
MH  - Amino Acid Substitution
MH  - Animals
MH  - *Cell Membrane/chemistry/genetics/metabolism
MH  - Cells, Cultured
MH  - Drosophila melanogaster
MH  - Extracellular Signal-Regulated MAP Kinases/chemistry/genetics/metabolism
MH  - Humans
MH  - Mice
MH  - Mice, Knockout
MH  - Mutation, Missense
MH  - Nuclear Magnetic Resonance, Biomolecular
MH  - *Phospholipids/chemistry/genetics/metabolism
MH  - Protein Binding/physiology
MH  - *Protein Kinases/chemistry/genetics/metabolism
MH  - Protein Structure, Tertiary
MH  - raf Kinases/chemistry/genetics/metabolism
PMC - PMC3740349
MID - NIHMS495192
COIS- Competing interest: The authors declare that they have no competing financial 
      interests.
EDAT- 2012/12/20 06:00
MHDA- 2013/05/28 06:00
PMCR- 2013/12/18
CRDT- 2012/12/20 06:00
PHST- 2012/12/20 06:00 [entrez]
PHST- 2012/12/20 06:00 [pubmed]
PHST- 2013/05/28 06:00 [medline]
PHST- 2013/12/18 00:00 [pmc-release]
AID - 5/255/ra94 [pii]
AID - 10.1126/scisignal.2003289 [doi]
PST - epublish
SO  - Sci Signal. 2012 Dec 18;5(255):ra94. doi: 10.1126/scisignal.2003289.