Abstract：
:Thromboxane A2 is a potent mediator of inflammation and platelet aggregation exerting its effects through the activation of a G protein-coupled receptor (GPCR), termed TP. Although the existence of dimers/oligomers in Class A GPCRs is widely accepted, their functional significance still remains controversial. Recently, we have shown that TPα and TPβ homo-/hetero-dimers interact through an interface of residues in transmembrane domain 1 (TM1) whose disruption impairs dimer formation. Here, biochemical and pharmacological characterization of this dimer deficient mutant (DDM) in living cells indicates a significant impairment in its response to agonists. Interestingly, two single loss-of-function TPα variants, namely W29C and N42S recently identified in two heterozygous patients affected by bleeding disorders, match some of the residues mutated in our DDM. These two naturally occurring variants display a reduced potency to TP agonists and are characterized by impaired dimer formation in transfected HEK-293T cells. These findings provide proofs that lack of homo-dimer formation is a crucial process for reduced TPα function in vivo, and might represent one molecular mechanism through which platelet TPα receptor dysfunction affects the patient(s) carrying these mutations.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Capra V,Mauri M,Guzzi F,Busnelli M,Accomazzo MR,Gaussem P,Nisar SP,Mundell SJ,Parenti M,Rovati GEdoi
10.1016/j.bcp.2016.11.010subject
Has Abstractpub_date
2017-01-15 00:00:00pages
43-56eissn
0006-2952issn
1873-2968pii
S0006-2952(16)30397-5journal_volume
124pub_type
杂志文章abstract：:This Festschrift contribution summarizes the perspectives of two of David Triggle's graduate students. Both share somewhat parallel scientific and career paths-i.e., enrolling in the Biochemical Pharmacology program at the University of Buffalo, pursuing graduate training under the mentorship of David Triggle and subs...
journal_title：Biochemical pharmacology
pub_type： 历史文章,杂志文章,评审
doi：10.1016/j.bcp.2015.08.002
更新日期：2015-11-15 00:00:00
abstract：:The major metabolic products of the endogeneous catecholamine dopamine are its 3- and 4-O-sulphates which have also been implicated as intermediates in noradrenaline biosynthesis. Because of the unsatisfactory status of the literature concerning the synthesis, isolation, purity and characterisation of the dopamine O-s...
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pub_type： 杂志文章
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2012.09.032
更新日期：2012-12-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90024-f
更新日期：1990-01-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
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pub_type： 杂志文章
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更新日期：2014-12-15 00:00:00
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pub_type： 杂志文章
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更新日期：2009-11-01 00:00:00
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pub_type： 杂志文章
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pub_type： 杂志文章
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90528-9
更新日期：1986-01-15 00:00:00
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pub_type： 杂志文章
doi：10.1016/0006-2952(95)00084-d
更新日期：1995-07-17 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(03)00043-1
更新日期：2003-04-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90671-x
更新日期：1987-12-15 00:00:00
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pub_type： 杂志文章
doi：10.1016/0006-2952(90)90498-a
更新日期：1990-09-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/0006-2952(89)90233-5
更新日期：1989-03-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/s0006-2952(00)00374-9
更新日期：2000-09-01 00:00:00
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pub_type： 杂志文章
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pub_type： 杂志文章
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更新日期：2019-08-01 00:00:00
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pub_type： 杂志文章
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pub_type： 杂志文章
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pub_type： 杂志文章
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pub_type： 杂志文章
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pub_type： 杂志文章
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更新日期：2009-03-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/0006-2952(91)90174-4
更新日期：1991-06-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2016.08.020
更新日期：2016-10-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90460-7
更新日期：1989-07-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(98)00330-x
更新日期：1999-04-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90719-1
更新日期：1985-10-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)00035-x
更新日期：1995-05-11 00:00:00
