Linked Life Data

9238862

Source:http://linkedlifedata.com/resource/pubmed/id/9238862

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1997-8-26
pubmed:abstractText
The LH/CG receptor is comprised of two structurally and functionally distinct domains, extracellular N-terminal exodomain and membrane-embedded endodomain. These two domains can separately be expressed and processed, including folding. The exodomain alone has the high-affinity hormone binding site but is not capable of generating hormonal signal. In contrast, the endodomain alone has the site for receptor activation. These two domains contact each other in holo-receptor and split receptor. This interaction, particularly through exoloops 2 and 3, constrains the high-affinity hormone binding at the exodomain. Conversely, the exodomain could be involved in receptor activation. Therefore, these two domains are not entirely independent, although they can be independently synthesized and processed. The existing evidence indicates that hCG and the receptor undergo multiple stages of interactions leading to receptor activation. Initial high-affinity binding of hCG to the exodomain results in conformational adjustments of the hCG/exodomain complex. This leads to the secondary, low-affinity contact of the hCG/exodomain complex with the endodomain. This secondary contact is responsible for generating signals. They are transduced through transmembrane domains (TM) to the cytoplasmic portion (cytoloops and the C-terminal tail) of the receptor and then transferred to cytoplasmic signaling molecules such as G protein. Mutations in the exodomain and endodomain (N-extension, exoloops, TM, cytoloops, and cytoplasmic tail) have the potential to interfere with receptor activation at different steps: signal generation, transduction, and transfer. Binding of hCG to the LH/CG receptor is known to induce two signals, one for adenylyl cyclase/ cAMP and the other for phospholipase C/inositol phosphate/diacylglycerol. The cAMP signal and IP signal diverge at the surface of the receptor. These independent signals are separately transduced through the transmembrane domains to the cytoplasmic part of the receptor, indicating the existence of the distinct transducers for each of the signals. Furthermore, it is likely that the divergent signals are separately transferred to cytoplasmic signal molecules such as G protein. In addition, each cAMP signal and IP signal consists of at least three separate subsignals: affinity signal, maximal production (efficacy) signal, and basal level signal. In heterodimeric hCG there are distinct parts responsible for high-affinity receptor binding and receptor activation. Particularly, the C-terminal residues of the alpha subunit play a crucial role in receptor activation. This alpha subunit is shared with other glycoprotein hormones, follicle-stimulating hormone, and thyroid-stimulating hormone. Interestingly, the alpha C-terminal residues play distinct roles in all three hormones, despite its common nature.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0079-9963
pubmed:author
pubmed:issnType
Print
pubmed:volume
52
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
431-53; discussion 454
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Interaction, signal generation, signal divergence, and signal transduction of LH/CG and the receptor.
pubmed:affiliation
Department of Molecular Biology, University of Wyoming, Laramie 82071-3944, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review