PMID- 11309393
OWN - NLM
STAT- MEDLINE
DCOM- 20010816
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 276
IP  - 26
DP  - 2001 Jun 29
TI  - Molecular determinants of the interaction between the inositol 
      1,4,5-trisphosphate receptor-associated cGMP kinase substrate (IRAG) and cGMP 
      kinase Ibeta.
PG  - 24153-9
AB  - Cyclic GMP-dependent protein kinase I (cGKI) affects the inositol 
      1,4,5-trisphosphate (InsP(3))-dependent release of intracellular calcium by 
      phosphorylation of IRAG (inositol 1,4,5-trisphophate receptor-associated cGMP 
      kinase substrate). IRAG is present in a macromolecular complex with the InsP(3) 
      receptor type I (InsP(3)RI) and cGKIbeta. The specificity of the interaction 
      between these three proteins was investigated by using the yeast two-hybrid 
      system and by co-precipitation of expressed proteins. The amino-terminal region 
      containing the leucine zipper (amino acids 1-53) of cGKIbeta but not that of 
      cGKIalpha or cGKII interacted with the sequence between amino acids 152 and 184 
      of IRAG in vitro and in vivo most likely through electrostatic interaction. 
      cGKIbeta did not interact with the InsP(3)RI, but co-precipitated the InsP(3)RI 
      in the presence of IRAG indicating that IRAG bound to the InsP(3)RI and to 
      cGKIbeta. cGKIbeta phosphorylated up to four serines in IRAG. Mutation of these 
      four serines to alanine showed that cGKIbeta-dependent phosphorylation of 
      Ser(696) is necessary to decrease calcium release from InsP(3)-sensitive stores. 
      These results show that cGMP induced reduction of cytosolic calcium 
      concentrations requires cGKIbeta and phosphorylation of Ser(696) of IRAG.
FAU - Ammendola, A
AU  - Ammendola A
AD  - Institut fur Pharmakologie und Toxikologie der Technischen Universitat Munchen, 
      Biedersteiner Strasse 29, D-80802 Munchen, Germany.
FAU - Geiselhoringer, A
AU  - Geiselhoringer A
FAU - Hofmann, F
AU  - Hofmann F
FAU - Schlossmann, J
AU  - Schlossmann J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20010417
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Calcium Channels)
RN  - 0 (Inositol 1,4,5-Trisphosphate Receptors)
RN  - 0 (Macromolecular Substances)
RN  - 0 (Phosphoproteins)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 17885-08-4 (Phosphoserine)
RN  - EC 2.7.11.12 (Cyclic GMP-Dependent Protein Kinases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - COS Cells
MH  - Calcium/metabolism
MH  - Calcium Channels/metabolism
MH  - Cyclic GMP-Dependent Protein Kinases/*chemistry/*metabolism
MH  - Inositol 1,4,5-Trisphosphate Receptors
MH  - Leucine Zippers
MH  - Macromolecular Substances
MH  - Phosphoproteins/*metabolism/physiology
MH  - Phosphorylation
MH  - Phosphoserine/metabolism
MH  - Protein Binding
MH  - Receptors, Cytoplasmic and Nuclear/metabolism
EDAT- 2001/04/20 10:00
MHDA- 2001/08/17 10:01
CRDT- 2001/04/20 10:00
PHST- 2001/04/20 10:00 [pubmed]
PHST- 2001/08/17 10:01 [medline]
PHST- 2001/04/20 10:00 [entrez]
AID - S0021-9258(20)78425-5 [pii]
AID - 10.1074/jbc.M101530200 [doi]
PST - ppublish
SO  - J Biol Chem. 2001 Jun 29;276(26):24153-9. doi: 10.1074/jbc.M101530200. Epub 2001 
      Apr 17.