Molecular characterization of an anchor protein (AKAP(CE)) that binds the RI subunit (R(CE)) of type I protein kinase a from Caenorhabditis elegans

Robert Angelo, Charles S. Rubin

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Abstract

Classical A kinase anchor proteins (AKAPs) preferentially tether type II protein kinase A (PKAII) isoforms to sites in the cytoskeleton and organelles. It is not known if distinct proteins selectively sequester regulatory (R) subunits of type I PKAs, thereby diversifying functions of these critical enzymes. In Caenorhabditis elegans, a single type I PKA mediates all aspects of cAMP signaling. We have discovered a cDNA that encodes a binding protein (AKAP(cE)) for the regulatory subunit (R(CE)) of C. elegans PKAI(CE). AKAP(CE) is a novel, highly acidic RING finger protein composed of 1,280 amino acids. It binds RI-like R(CE) with high affinity and neither RIIα nor RIIβ competitively inhibits formation of AKAP(CE)®(CE)) complexes. The R(CE)-binding site was mapped to a segment of 20 amino acids in an N-terminal region of AKAP(CE). Several hydrophobic residues in the binding site align with essential Leu and He residues in the RII-selective tethering domain of prototypic mammalian AKAPs. However, the R(CE)-binding region in AKAP(CE) diverges sharply from consensus RII-binding sites by inclusion of three aromatic amino acids, exclusion of a highly conserved Leu or Ile at position 8 and replacement of C-terminal hydrophobic amino acids with basic residues. AKAP(CE)·R(CE) complexes accumulate in intact cells.

Original languageEnglish (US)
Pages (from-to)14633-14643
Number of pages11
JournalJournal of Biological Chemistry
Volume273
Issue number23
DOIs
StatePublished - Jun 5 1998

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A Kinase Anchor Proteins
Caenorhabditis elegans Proteins
Caenorhabditis elegans
Anchors
Protein Kinases
Proteins
Binding Sites
Amino Acids
Cyclic AMP-Dependent Protein Kinase Type II
Aromatic Amino Acids
Staphylococcal Protein A
Carrier Proteins
Protein Isoforms
Basic Amino Acids
Complementary DNA
A kinase anchor protein (kap-1), C elegans
Cytoskeleton
Organelles
Enzymes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Molecular characterization of an anchor protein (AKAP(CE)) that binds the RI subunit (R(CE)) of type I protein kinase a from Caenorhabditis elegans. / Angelo, Robert; Rubin, Charles S.

In: Journal of Biological Chemistry, Vol. 273, No. 23, 05.06.1998, p. 14633-14643.

Research output: Contribution to journalArticle

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