PMID- 10613906
OWN - NLM
STAT- MEDLINE
DCOM- 20000204
LR  - 20191023
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 147
IP  - 7
DP  - 1999 Dec 27
TI  - Alternative splicing regulates the subcellular localization of A-kinase anchoring
      protein 18 isoforms.
PG  - 1481-92
AB  - The cAMP-dependent protein kinase (PKA) is localized to specific subcellular
      compartments by association with A-kinase anchoring proteins (AKAPs). AKAPs are a
      family of functionally related proteins that bind the regulatory (R) subunit of
      PKA with high affinity and target the kinase to specific subcellular organelles. 
      Recently, AKAP18, a low molecular weight plasma membrane AKAP that facilitates
      PKA-mediated phosphorylation of the L-type Ca(2+) channel, was cloned. We now
      report the cloning of two additional isoforms of AKAP18, which we have designated
      AKAP18beta and AKAP18gamma, that arise from alternative mRNA splicing. The AKAP18
      isoforms share a common R subunit binding site, but have distinct targeting
      domains. The original AKAP18 (renamed AKAP18alpha) and AKAP18beta target the
      plasma membrane when expressed in HEK-293 cells, while AKAP18gamma is cytosolic. 
      When expressed in epithelial cells, AKAP18alpha is targeted to lateral membranes,
      whereas AKAP18beta is accumulated at the apical membrane. A 23-amino acid insert,
      following the plasma membrane targeting domain, facilitates the association of
      AKAP18beta with the apical membrane. The data suggest that AKAP18 isoforms are
      differentially targeted to modulate distinct intracellular signaling events.
      Furthermore, the data suggest that plasma membrane AKAPs may be targeted to
      subdomains of the cell surface, adding additional specificity in intracellular
      signaling.
FAU - Trotter, K W
AU  - Trotter KW
AD  - Department of Cell and Molecular Physiology, The University of North Carolina at 
      Chapel Hill, Chapel Hill, North Carolina 27599, USA.
FAU - Fraser, I D
AU  - Fraser ID
FAU - Scott, G K
AU  - Scott GK
FAU - Stutts, M J
AU  - Stutts MJ
FAU - Scott, J D
AU  - Scott JD
FAU - Milgram, S L
AU  - Milgram SL
LA  - eng
SI  - GENBANK/AF152929
SI  - GENBANK/AF161075
GR  - HL60280/HL/NHLBI NIH HHS/United States
GR  - GM48231/GM/NIGMS 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 (AKAP7 protein, human)
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Protein Isoforms)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
SB  - IM
MH  - A Kinase Anchor Proteins
MH  - *Adaptor Proteins, Signal Transducing
MH  - Alternative Splicing/*physiology
MH  - Amino Acid Sequence
MH  - Animals
MH  - COS Cells
MH  - Carrier Proteins/*genetics/*metabolism
MH  - Cell Line
MH  - Cell Polarity/genetics
MH  - Cloning, Molecular
MH  - Cyclic AMP-Dependent Protein Kinases/*metabolism
MH  - Dogs
MH  - Epithelial Cells/metabolism
MH  - Humans
MH  - *Membrane Proteins
MH  - Molecular Sequence Data
MH  - Protein Isoforms/genetics/metabolism
MH  - Rats
MH  - Subcellular Fractions/enzymology
PMC - PMC2174236
EDAT- 1999/12/30 00:00
MHDA- 1999/12/30 00:01
CRDT- 1999/12/30 00:00
PHST- 1999/12/30 00:00 [pubmed]
PHST- 1999/12/30 00:01 [medline]
PHST- 1999/12/30 00:00 [entrez]
AID - 10.1083/jcb.147.7.1481 [doi]
PST - ppublish
SO  - J Cell Biol. 1999 Dec 27;147(7):1481-92. doi: 10.1083/jcb.147.7.1481.