PMID- 10101032
OWN - NLM
STAT- MEDLINE
DCOM- 19990420
LR  - 20131121
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 55
IP  - 4
DP  - 1999 Apr
TI  - Identification of protein kinase C phosphorylation sites involved in phorbol
      ester-induced desensitization of the histamine H1 receptor.
PG  - 735-42
AB  - The histamine H1 receptor (H1R)-mediated signaling cascade is inhibited by
      phorbol ester-induced protein kinase C (PKC) activation. Cloning studies of the
      H1Rs have shown that several potential PKC phosphorylation sites are located in
      the third intracellular loop of H1R. To elucidate the molecular mechanism of
      PKC-mediated desensitization, we identified amino acid residues that are involved
      in the desensitization of the H1R. Two amino acid residues (Ser396, Ser398) were 
      determined to be PKC phosphorylation sites by in vitro phosphorylation studies
      using a series of synthetic peptides. Treatment with phorbol ester decreased
      histamine-induced accumulation of inositol phosphates in Chinese hamster ovary
      cells expressing the H1R with a rightward shift in the EC50 value, which implies 
      the uncoupling of the receptor from the G protein. Site-directed mutagenesis
      studies showed that substitution of alanine for Ser398 but not for Ser396
      markedly attenuated the effect of phorbol ester, which suggests that the Ser398
      residue was primarily involved in PKC-mediated desensitization.
FAU - Fujimoto, K
AU  - Fujimoto K
AD  - School of Allied Health Science, Faculty of Medicine, Osaka University, Suita,
      Japan.
FAU - Ohta, K
AU  - Ohta K
FAU - Kangawa, K
AU  - Kangawa K
FAU - Kikkawa, U
AU  - Kikkawa U
FAU - Ogino, S
AU  - Ogino S
FAU - Fukui, H
AU  - Fukui H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, Histamine H1)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - CHO Cells
MH  - Cricetinae
MH  - Humans
MH  - Molecular Sequence Data
MH  - Mutation/drug effects
MH  - Peptide Fragments/metabolism
MH  - Phosphorylation
MH  - Protein Kinase C/*metabolism
MH  - Receptors, Histamine H1/genetics/*metabolism
MH  - Sequence Homology, Amino Acid
MH  - Serine/metabolism
MH  - Tetradecanoylphorbol Acetate/pharmacology
EDAT- 1999/04/01 00:00
MHDA- 1999/04/01 00:01
CRDT- 1999/04/01 00:00
PHST- 1999/04/01 00:00 [pubmed]
PHST- 1999/04/01 00:01 [medline]
PHST- 1999/04/01 00:00 [entrez]
PST - ppublish
SO  - Mol Pharmacol. 1999 Apr;55(4):735-42.