PMID- 10352013
OWN - NLM
STAT- MEDLINE
DCOM- 19990701
LR  - 20190508
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 145
IP  - 5
DP  - 1999 May 31
TI  - NH2-Terminal targeting motifs direct dual specificity A-kinase-anchoring protein 
      1 (D-AKAP1) to either mitochondria or endoplasmic reticulum.
PG  - 951-9
AB  - Subcellular localization directed by specific targeting motifs is an emerging
      theme for regulating signal transduction pathways. For cAMP-dependent protein
      kinase (PKA), this is achieved primarily by its association with
      A-kinase-anchoring proteins (AKAPs). Dual specificity AKAP1, (D-AKAP1) binds to
      both type I and type II regulatory subunits and has two NH2-terminal (N0 and N1) 
      and two COOH-terminal (C1 and C2) splice variants (. J. Biol. Chem. 272:8057).
      Here we report that the splice variants of D-AKAP1 are expressed in a
      tissue-specific manner with the NH2-terminal motifs serving as switches to
      localize D-AKAP1 at different sites. Northern blots showed that the N1 splice is 
      expressed primarily in liver, while the C1 splice is predominant in testis. The
      C2 splice shows a general expression pattern. Microinjecting expression
      constructs of D-AKAP1(N0) epitope-tagged at either the NH2 or the COOH terminus
      showed their localization to the mitochondria based on immunocytochemistry.
      Deletion of N0(1-30) abolished mitochondrial targeting while N0(1-30)-GFP
      localized to mitochondria. Residues 1-30 of N0 are therefore necessary and
      sufficient for mitochondria targeting. Addition of the 33 residues of N1 targets 
      D-AKAP1 to the ER and residues 1-63 fused to GFP are necessary and sufficient for
      ER targeting. Residues 14-33 of N1 are especially important for targeting to ER; 
      however, residues 1-33 alone fused to GFP gave a diffuse distribution. N1(14-33) 
      thus serves two functions: (a) it suppresses the mitochondrial-targeting motif
      located within residues 1-30 of N0 and (b) it exposes an ER-targeting motif that 
      is at least partially contained within the N0(1-30) motif. This represents the
      first example of a differentially targeted AKAP and adds an additional level of
      complexity to the PKA signaling network.
FAU - Huang, L J
AU  - Huang LJ
AD  - Howard Hughes Medical Institute, Department of Chemistry and Biochemistry,
      University of California, San Diego, La Jolla, California 92093-0654, USA.
FAU - Wang, L
AU  - Wang L
FAU - Ma, Y
AU  - Ma Y
FAU - Durick, K
AU  - Durick K
FAU - Perkins, G
AU  - Perkins G
FAU - Deerinck, T J
AU  - Deerinck TJ
FAU - Ellisman, M H
AU  - Ellisman MH
FAU - Taylor, S S
AU  - Taylor SS
LA  - eng
GR  - RR04050/RR/NCRR NIH HHS/United States
GR  - P01 DK054441/DK/NIDDK NIH HHS/United States
GR  - 2T32GM07240-21-21A1/GM/NIGMS NIH HHS/United States
GR  - T32 GM007240/GM/NIGMS NIH HHS/United States
GR  - P41 RR004050/RR/NCRR NIH HHS/United States
GR  - 1PO1DK54441-01/DK/NIDDK NIH HHS/United States
GR  - T32 CA009523/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 Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (A Kinase Anchor Proteins)
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Akap1 protein, mouse)
RN  - 0 (Carrier Proteins)
SB  - IM
MH  - A Kinase Anchor Proteins
MH  - *Adaptor Proteins, Signal Transducing
MH  - Amino Acid Sequence
MH  - Animals
MH  - Biological Transport
MH  - Carrier Proteins/chemistry/genetics/*metabolism
MH  - Cell Line
MH  - Cell-Free System
MH  - Endoplasmic Reticulum/*metabolism
MH  - Fibroblasts/*metabolism/*ultrastructure
MH  - Mice
MH  - Mitochondria/*metabolism
MH  - Molecular Sequence Data
MH  - RNA Splicing
MH  - Structure-Activity Relationship
PMC - PMC2133123
EDAT- 1999/06/03 00:00
MHDA- 1999/06/03 00:01
CRDT- 1999/06/03 00:00
PHST- 1999/06/03 00:00 [pubmed]
PHST- 1999/06/03 00:01 [medline]
PHST- 1999/06/03 00:00 [entrez]
AID - 10.1083/jcb.145.5.951 [doi]
PST - ppublish
SO  - J Cell Biol. 1999 May 31;145(5):951-9. doi: 10.1083/jcb.145.5.951.