| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 276, Issue 16, 12938-12944, April 20, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the The expression of the paracrine signaling hormone
pituitary adenylate
cyclase-activating polypeptide
(PACAP) is regulated in a cyclical fashion during the 12-day
spermatogenic cycle of the adult rat testis. The precise functions of
PACAP in the development of germ cells are uncertain, but cycle-
and stage-specific expression may augment cAMP-regulated gene
expression in germ cells and associated Sertoli cells. Here we report
the existence of a heretofore unrecognized exon in the extracellular
domain of the PACAP type 1 receptor (PAC1R) that is alternatively
spliced during the spermatogenic cycle in the rat testis. This splice
variant encodes a full-length receptor with the insertion of an
additional 72 base pairs encoding 24 amino acids (exon 3a)
between coding exons 3 and 4. The PAC1R(3a) mRNA is preferentially
detected in seminiferous tubules and is expressed at the highest levels
in round spermatids and Sertoli cells. Analyses of ligand binding and
signaling functions in stably transfected HEK293 cells expressing the
two receptor isoforms reveals a 6-fold increase in the affinity of the
PAC1R(3a) to bind PACAP-38, and alterations in its coupling to both
cAMP and inositol phosphate signaling pathways relative to the wild
type PAC1R. These findings suggest that the extracellular region
between coding exons 3 and 6 of PAC1R may play an important role in the regulation of the relative ligand affinities and the relative coupling
to Gs (cAMP) and Gq (inositol phosphates)
signal transduction pathways during spermatogenesis.
Novel Alternatively Spliced Exon in the Extracellular
Ligand-binding Domain of the Pituitary Adenylate Cyclase-activating
Polypeptide (PACAP) Type 1 Receptor (PAC1R) Selectively
Increases Ligand Affinity and Alters Signal Transduction Coupling
during Spermatogenesis*
§,¶,, and
Laboratory of Molecular Endocrinology,
Massachusetts General Hospital, Howard Hughes Medical Institute,
Harvard Medical School, Boston, Massachusetts 02114
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Laboratory of
Molecular Endocrinology, Massachusetts General Hospital, 55 Fruit St.,
WEL320, Boston, MA 02114. Tel.: 617-726-5190; Fax: 617-726-6954; E-mail:
jhabener@partners.org.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Ushiyama, R. Ikeda, H. Sugawara, M. Yoshida, K. Mori, K. Kangawa, K. Inoue, K. Yamada, and A. Miyata Differential Intracellular Signaling through PAC1 Isoforms as a Result of Alternative Splicing in the First Extracellular Domain and the Third Intracellular Loop Mol. Pharmacol., July 1, 2007; 72(1): 103 - 111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Mustafa, M. Grimaldi, and L. E. Eiden The Hop Cassette of the PAC1 Receptor Confers Coupling to Ca2+ Elevation Required for Pituitary Adenylate Cyclase-activating Polypeptide-evoked Neurosecretion J. Biol. Chem., March 16, 2007; 282(11): 8079 - 8091. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Delgado, D. Pozo, and D. Ganea The Significance of Vasoactive Intestinal Peptide in Immunomodulation Pharmacol. Rev., June 1, 2004; 56(2): 249 - 290. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Reubi Peptide Receptors as Molecular Targets for Cancer Diagnosis and Therapy Endocr. Rev., August 1, 2003; 24(4): 389 - 427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Bouschet, V. Perez, C. Fernandez, J. Bockaert, A. Eychene, and L. Journot Stimulation of the ERK Pathway by GTP-loaded Rap1 Requires the Concomitant Activation of Ras, Protein Kinase C, and Protein Kinase A in Neuronal Cells J. Biol. Chem., February 7, 2003; 278(7): 4778 - 4785. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Alexandre, H. Vaudry, L. Grumolato, V. Turquier, A. Fournier, S. Jegou, and Y. Anouar Novel Splice Variants of Type I Pituitary Adenylate Cyclase-Activating Polypeptide Receptor in Frog Exhibit Altered Adenylate Cyclase Stimulation and Differential Relative Abundance Endocrinology, July 1, 2002; 143(7): 2680 - 2692. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
