PMID- 10220570
OWN - NLM
STAT- MEDLINE
DCOM- 19990601
LR  - 20131121
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 55
IP  - 5
DP  - 1999 May
TI  - Novel brain-specific 5-HT4 receptor splice variants show marked constitutive
      activity: role of the C-terminal intracellular domain.
PG  - 910-20
AB  - We have cloned new 5-Hydroxytryptamine 4 (5-HT4) receptor splice variants from
      mouse (m5-HT4(e)R and m5-HT4(f)R), rat (r5-HT4(e)R), and human brain tissue
      (h5-HT4(e)R) which differ, as do the previously described 5-HT4 receptor
      variants, in the length and composition of their intracellular C termini after
      the common splicing site (L358). These new variants have a unique C-terminal
      sequence made of two PV repeats and are only expressed in brain tissue. All of
      the 5-HT4 receptor splice variants have a high constitutive activity when
      expressed at low and physiological densities (<500 fmol/mg protein). At similar
      density, they showed a much higher constitutive activity than the native and the 
      mutated beta2-adrenergic receptors. The constitutive activity of the new splice
      variants with short C-terminal sequences (m5-HT4(e)R and m5-HT4(f)R) was higher
      than that of the long C-terminal sequence variants (m5-HT4(a)R and m5-HT4(b)R).
      This may indicate that the short variants have a higher capacity for
      isomerization from the inactive to the active conformation. Moreover, we further 
      identified a sequence within the C-terminal tail upstream of L358, rich in serine
      and threonine residues, that played a crucial role in maintaining 5-HT4R under
      its inactive conformation.
FAU - Claeysen, S
AU  - Claeysen S
AD  - Centre National de la Recherche Scientifique, Unite Propre de Recherche 9023,
      Montpellier, France.
FAU - Sebben, M
AU  - Sebben M
FAU - Becamel, C
AU  - Becamel C
FAU - Bockaert, J
AU  - Bockaert J
FAU - Dumuis, A
AU  - Dumuis A
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 (Receptors, Adrenergic, beta)
RN  - 0 (Receptors, Serotonin)
RN  - 158165-40-3 (Receptors, Serotonin, 5-HT4)
RN  - 333DO1RDJY (Serotonin)
RN  - E0399OZS9N (Cyclic AMP)
SB  - IM
MH  - *Alternative Splicing
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Animals
MH  - Brain/metabolism
MH  - Cells, Cultured
MH  - Cyclic AMP/biosynthesis
MH  - Gene Deletion
MH  - Humans
MH  - Mice
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Protein Conformation
MH  - Rats
MH  - Receptors, Adrenergic, beta/genetics
MH  - Receptors, Serotonin/chemistry/*genetics
MH  - Receptors, Serotonin, 5-HT4
MH  - Sequence Homology, Amino Acid
MH  - Serotonin/metabolism
EDAT- 1999/04/30 00:00
MHDA- 1999/04/30 00:01
CRDT- 1999/04/30 00:00
PHST- 1999/04/30 00:00 [pubmed]
PHST- 1999/04/30 00:01 [medline]
PHST- 1999/04/30 00:00 [entrez]
PST - ppublish
SO  - Mol Pharmacol. 1999 May;55(5):910-20.