Molecular characterization of a cDNA that encodes six isoforms of a novel murine a kinase anchor protein

Feng Dong, Marta Feldmesser, Arturo Casadevall, Charles S. Rubin

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

We have cloned cDNA that encodes six novel A kinase anchor proteins (collectively named AKAP-KL). AKAP-KL diversity is generated by alternative mRNA splicing and utilization of two translation initiation codons. AKAP-KL polypeptides are evident in lung, kidney, and cerebellum, but are absent from many tissues. Different isoforms predominate in different tissues. Thus, AKAP-KL expression is differentially regulated in vivo. All AKAP-KL isoforms contain a 20-residue domain that avidly binds (K(d) ~ 10 nM) regulatory subunits (RII) of protein kinase AII and is highly homologous with the RII tethering site in neuronal AKAP75. The distribution of AKAP-KL is strikingly asymmetric (polarized) in situ. Anchor protein accumulates near the inner, apical surface of highly polarized epithelium in tubules of nephrons. Both RII and AKAP-KL are enriched at an intracellular site that lies just below the plasma membrane of alveolar epithelial cells in lung. AKAP-KL interacts with and modulates the structure of the actin cytoskeleton in transfected cells. We also demonstrate that the tethering domain of AKAP-KL avidly ligates RII subunits in intact cells. AKAP-KL may be involved in (a) establishing polarity in signaling systems and (b) physically and functionally integrating PKAII isoforms with downstream effectors to capture, amplify, and precisely focus diffuse, trans-cellular signals carried by cAMP.

Original languageEnglish (US)
Pages (from-to)6533-6541
Number of pages9
JournalJournal of Biological Chemistry
Volume273
Issue number11
DOIs
StatePublished - Mar 13 1998

Fingerprint

Anchors
Protein Kinases
Protein Isoforms
Phosphotransferases
Complementary DNA
A Kinase Anchor Proteins
Tissue
Alveolar Epithelial Cells
Lung
Proteins
Initiator Codon
Nephrons
Alternative Splicing
Cell membranes
Actin Cytoskeleton
Cerebellum
Actins
Epithelium
Cell Membrane
Kidney

ASJC Scopus subject areas

  • Biochemistry

Cite this

Molecular characterization of a cDNA that encodes six isoforms of a novel murine a kinase anchor protein. / Dong, Feng; Feldmesser, Marta; Casadevall, Arturo; Rubin, Charles S.

In: Journal of Biological Chemistry, Vol. 273, No. 11, 13.03.1998, p. 6533-6541.

Research output: Contribution to journalArticle

Dong, Feng ; Feldmesser, Marta ; Casadevall, Arturo ; Rubin, Charles S. / Molecular characterization of a cDNA that encodes six isoforms of a novel murine a kinase anchor protein. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 11. pp. 6533-6541.
@article{1217021a89b44363bed0d901035874c0,
title = "Molecular characterization of a cDNA that encodes six isoforms of a novel murine a kinase anchor protein",
abstract = "We have cloned cDNA that encodes six novel A kinase anchor proteins (collectively named AKAP-KL). AKAP-KL diversity is generated by alternative mRNA splicing and utilization of two translation initiation codons. AKAP-KL polypeptides are evident in lung, kidney, and cerebellum, but are absent from many tissues. Different isoforms predominate in different tissues. Thus, AKAP-KL expression is differentially regulated in vivo. All AKAP-KL isoforms contain a 20-residue domain that avidly binds (K(d) ~ 10 nM) regulatory subunits (RII) of protein kinase AII and is highly homologous with the RII tethering site in neuronal AKAP75. The distribution of AKAP-KL is strikingly asymmetric (polarized) in situ. Anchor protein accumulates near the inner, apical surface of highly polarized epithelium in tubules of nephrons. Both RII and AKAP-KL are enriched at an intracellular site that lies just below the plasma membrane of alveolar epithelial cells in lung. AKAP-KL interacts with and modulates the structure of the actin cytoskeleton in transfected cells. We also demonstrate that the tethering domain of AKAP-KL avidly ligates RII subunits in intact cells. AKAP-KL may be involved in (a) establishing polarity in signaling systems and (b) physically and functionally integrating PKAII isoforms with downstream effectors to capture, amplify, and precisely focus diffuse, trans-cellular signals carried by cAMP.",
author = "Feng Dong and Marta Feldmesser and Arturo Casadevall and Rubin, {Charles S.}",
year = "1998",
month = "3",
day = "13",
doi = "10.1074/jbc.273.11.6533",
language = "English (US)",
volume = "273",
pages = "6533--6541",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "11",

}

TY - JOUR

T1 - Molecular characterization of a cDNA that encodes six isoforms of a novel murine a kinase anchor protein

AU - Dong, Feng

AU - Feldmesser, Marta

AU - Casadevall, Arturo

AU - Rubin, Charles S.

PY - 1998/3/13

Y1 - 1998/3/13

N2 - We have cloned cDNA that encodes six novel A kinase anchor proteins (collectively named AKAP-KL). AKAP-KL diversity is generated by alternative mRNA splicing and utilization of two translation initiation codons. AKAP-KL polypeptides are evident in lung, kidney, and cerebellum, but are absent from many tissues. Different isoforms predominate in different tissues. Thus, AKAP-KL expression is differentially regulated in vivo. All AKAP-KL isoforms contain a 20-residue domain that avidly binds (K(d) ~ 10 nM) regulatory subunits (RII) of protein kinase AII and is highly homologous with the RII tethering site in neuronal AKAP75. The distribution of AKAP-KL is strikingly asymmetric (polarized) in situ. Anchor protein accumulates near the inner, apical surface of highly polarized epithelium in tubules of nephrons. Both RII and AKAP-KL are enriched at an intracellular site that lies just below the plasma membrane of alveolar epithelial cells in lung. AKAP-KL interacts with and modulates the structure of the actin cytoskeleton in transfected cells. We also demonstrate that the tethering domain of AKAP-KL avidly ligates RII subunits in intact cells. AKAP-KL may be involved in (a) establishing polarity in signaling systems and (b) physically and functionally integrating PKAII isoforms with downstream effectors to capture, amplify, and precisely focus diffuse, trans-cellular signals carried by cAMP.

AB - We have cloned cDNA that encodes six novel A kinase anchor proteins (collectively named AKAP-KL). AKAP-KL diversity is generated by alternative mRNA splicing and utilization of two translation initiation codons. AKAP-KL polypeptides are evident in lung, kidney, and cerebellum, but are absent from many tissues. Different isoforms predominate in different tissues. Thus, AKAP-KL expression is differentially regulated in vivo. All AKAP-KL isoforms contain a 20-residue domain that avidly binds (K(d) ~ 10 nM) regulatory subunits (RII) of protein kinase AII and is highly homologous with the RII tethering site in neuronal AKAP75. The distribution of AKAP-KL is strikingly asymmetric (polarized) in situ. Anchor protein accumulates near the inner, apical surface of highly polarized epithelium in tubules of nephrons. Both RII and AKAP-KL are enriched at an intracellular site that lies just below the plasma membrane of alveolar epithelial cells in lung. AKAP-KL interacts with and modulates the structure of the actin cytoskeleton in transfected cells. We also demonstrate that the tethering domain of AKAP-KL avidly ligates RII subunits in intact cells. AKAP-KL may be involved in (a) establishing polarity in signaling systems and (b) physically and functionally integrating PKAII isoforms with downstream effectors to capture, amplify, and precisely focus diffuse, trans-cellular signals carried by cAMP.

UR - http://www.scopus.com/inward/record.url?scp=0032513054&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032513054&partnerID=8YFLogxK

U2 - 10.1074/jbc.273.11.6533

DO - 10.1074/jbc.273.11.6533

M3 - Article

C2 - 9497389

AN - SCOPUS:0032513054

VL - 273

SP - 6533

EP - 6541

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 11

ER -