A constitutively activating mutation of the luteinizing hormone receptor in familial male precocious puberty
Andrew Shenker,Laue L,Shinji Kosugi,Shinji Kosugi,John J. Merendino,Takashi Minegishi,Gordon B. Cutler +6 more
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COS-7 cells expressing the mutant LH receptor exhibited markedly increased cyclic AMP production in the absence of agonist, suggesting that autonomous Leydig cell activity in FMPP is caused by a constitutively activated LH receptor.Abstract:
Familial male precocious puberty (FMPP) is a gonadotropin-independent disorder that is inherited in an autosomal dominant, male-limited pattern. Affected males generally exhibit signs of puberty by age 4. Testosterone production and Leydig cell hyperplasia occur in the context of prepubertal levels of luteinizing hormone (LH). The LH receptor is a member of the family of G-protein-coupled receptors, and we hypothesized that FMPP might be due to a mutant receptor that is activated in the presence of little or no agonist. A single A-->G base change that results in substitution of glycine for aspartate at position 578 in the sixth transmembrane helix of the LH receptor was found in affected individuals from eight different families. Linkage of the mutation to FMPP was supported by restriction-digest analysis. COS-7 cells expressing the mutant LH receptor exhibited markedly increased cyclic AMP production in the absence of agonist, suggesting that autonomous Leydig cell activity in FMPP is caused by a constitutively activated LH receptor.read more
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Uncovering Molecular Mechanisms Involved in Activation of G Protein-Coupled Receptors
TL;DR: The goal of the present review is to specifically address the physical changes linking agonist binding to receptor activation and subsequent transduction of the signal to the associated G protein on the cytoplasmic side of the membrane and to other putative signaling pathways.
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Mammalian G proteins and their cell type specific functions
TL;DR: In this review, some of the functions of heterotrimeric G proteins in defined cells and tissues are described.
Journal ArticleDOI
Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity : possible implications for opiate addiction
Cherie E. Bond,K. Steven LaForge,Mingting Tian,Dorothy Melia,Shengwen Zhang,Lisa Borg,Jianhua Gong,James H. Schluger,Judith A. Strong,Suzanne M. Leal,Jay A. Tischfield,Mary Jeanne Kreek,Lei Yu +12 more
TL;DR: Results show that SNPs in the mu opioid receptor gene can alter binding and signal transduction in the resulting receptor and may have implications for normal physiology, therapeutics, and vulnerability to develop or protection from diverse diseases including the addictive diseases.
Journal ArticleDOI
G-protein-coupled receptors and signaling networks: emerging paradigms.
TL;DR: Effectors for GPCRs that are independent of G proteins have now also been identified, thus changing the conventional view of the GPCR-heterotrimeric-G-protein-associated effector.
Journal ArticleDOI
Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure
Kristiina Aittomäki,Kristiina Aittomäki,JoséLuis Dieguez Lucena,JoséLuis Dieguez Lucena,Pirjo Pakarinen,Pertti Sistonen,Juha S. Tapanainen,Jörg Gromoll,Riitta Kaskikari,Eeva-Marja Sankila,Heikki Lehväslaiho,Armando Reyes Engel,Eberhard Nieschlag,Ilpo Huhtaniemi,Albert de la Chapelle +14 more
TL;DR: It is concluded that a mutation in the follicle-stimulating hormone receptor gene causes hypergonadotropic ovarian dysgenesis in multiplex affected families and that the mutation causes ODG in these families.
References
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A mutation-induced activated state of the beta 2-adrenergic receptor. Extending the ternary complex model.
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Pigmentation phenotypes of variant extension locus alleles result from point mutations that alter MSH receptor function
Linda S. Robbins,Joseph H. Nadeau,Kenneth R. Johnson,Michele A. Kelly,Linda Roselli-Rehfuss,Eric Baack,Kathleen G. Mountjoy,Roger D. Cone +7 more
TL;DR: It is shown here that the murine extension locus encodes the melanocyte-stimulating hormone (MSH) receptor, and that the Eso-3J receptor is constitutively activated, while the Etob receptor remains hormone responsive and produces a greater activation of its effector than does the wild-type allele.