PMID- 10075657
OWN - NLM
STAT- MEDLINE
DCOM- 19990415
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 12
DP  - 1999 Mar 19
TI  - Interactions between neurogranin and calmodulin in vivo.
PG  - 7689-94
AB  - Neurogranin is a neural-specific, calmodulin (CaM)-binding protein that is
      phosphorylated by protein kinase C (PKC) within its IQ domain at serine 36. Since
      CaM binds to neurogranin through the IQ domain, PKC phosphorylation and CaM
      binding are mutually exclusive. Consequently, we hypothesize that neurogranin may
      function to concentrate CaM at specific sites in neurons and release free CaM in 
      response to increased Ca2+ and PKC activation. However, it has not been
      established that neurogranin interacts with CaM in vivo. In this study, we
      examined this question using yeast two-hybrid methodology. We also searched for
      additional proteins that might interact with neurogranin by screening brain cDNA 
      libraries. Our data illustrate that CaM binds to neurogranin in vivo and that CaM
      is the only neurogranin-interacting protein isolated from brain cDNA libraries.
      Single amino acid mutagenesis indicated that residues within the IQ domain are
      important for CaM binding to neurogranin in vivo. The Ile-33 --> Gln point mutant
      completely inhibited and Arg-38 --> Gln and Ser-36 --> Asp point mutants reduced 
      neurogranin/CaM interactions. These data demonstrate that CaM is the major
      protein that interacts with neurogranin in vivo and support the hypothesis that
      phosphorylation of neurogranin at Ser-36 regulates its binding to CaM.
FAU - Prichard, L
AU  - Prichard L
AD  - Department of Pharmacology, University of Washington, Seattle, Washington 98195, 
      USA.
FAU - Deloulme, J C
AU  - Deloulme JC
FAU - Storm, D R
AU  - Storm DR
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Adenylyl Cyclase Inhibitors)
RN  - 0 (Calmodulin)
RN  - 0 (Calmodulin-Binding Proteins)
RN  - 0 (NRGN protein, human)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Nrgn protein, mouse)
RN  - 0 (Nrgn protein, rat)
RN  - 132654-77-4 (Neurogranin)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adenylyl Cyclase Inhibitors
MH  - Amino Acid Substitution
MH  - Animals
MH  - Binding Sites
MH  - Calcium/metabolism
MH  - Calmodulin/*metabolism
MH  - Calmodulin-Binding Proteins/*metabolism
MH  - Cells, Cultured
MH  - Humans
MH  - Mice
MH  - Mutagenesis, Site-Directed
MH  - Nerve Tissue Proteins/*metabolism
MH  - Neurogranin
MH  - Phosphorylation
MH  - Point Mutation
MH  - Protein Kinase C/metabolism
MH  - Rats
MH  - Serine/metabolism
EDAT- 1999/03/13 00:00
MHDA- 1999/03/13 00:01
CRDT- 1999/03/13 00:00
PHST- 1999/03/13 00:00 [pubmed]
PHST- 1999/03/13 00:01 [medline]
PHST- 1999/03/13 00:00 [entrez]
AID - 10.1074/jbc.274.12.7689 [doi]
AID - S0021-9258(19)87460-4 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Mar 19;274(12):7689-94. doi: 10.1074/jbc.274.12.7689.