scholarly journals Constitutive stimulatory G protein activity in limb mesenchyme impairs bone growth

Bone ◽  
2018 ◽  
Vol 110 ◽  
pp. 230-237 ◽  
Author(s):  
Anara Karaca ◽  
Vijayram Reddy Malladi ◽  
Yan Zhu ◽  
Olta Tafaj ◽  
Elena Paltrinieri ◽  
...  
Keyword(s):  
G Protein ◽  
Bone Growth ◽  
Protein Activity ◽  
Limb Mesenchyme ◽  
Stimulatory G Protein

scholarly journals Density-dependent nerve growth factor regulation of Gs-alpha RNA in pheochromocytoma 12 cells.

1990 ◽  
Vol 10 (6) ◽  
pp. 3277-3279 ◽  
Author(s):  
G Tjaden ◽  
A Aguanno ◽  
R Kumar ◽  
D Benincasa ◽  
R M Gubits ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
G Protein ◽  
Alpha Subunit ◽  
Low Density ◽  
Dependent Manner ◽  
Nerve Growth ◽  
Density Dependent ◽  
Stimulatory G Protein ◽  
Gs Alpha

Nerve growth factor (NGF) affects levels of the alpha subunit of the stimulatory G protein (Gs-alpha) in pheochromocytoma 12 cells in a bidirectional, density-dependent manner. Cells grown at high density responded to NGF treatment with increased levels of Gs-alpha mRNA and protein. Conversely, in cells grown in low-density cultures, levels of this mRNA were lowered by NGF treatment.

scholarly journals Patients with Mutations in Gsα Have Reduced Activation of a Downstream Target in Epithelial Tissues due to Haploinsufficiency

2007 ◽  
Vol 92 (10) ◽  
pp. 3941-3948
Author(s):  
Stephanie C. Hsu ◽  
Joshua D. Groman ◽  
Christian A. Merlo ◽  
Kathleen Naughton ◽  
Pamela L. Zeitlin ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
G Protein ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Downstream Target ◽  
Epithelial Tissues ◽  
Stimulatory G Protein ◽  
Normal Controls

Abstract Context: Patients with Albright hereditary osteodystrophy (AHO) have defects in stimulatory G protein signaling due to loss of function mutations in GNAS. The mechanism by which these mutations lead to the AHO phenotype has been difficult to establish due to the inaccessibility of the affected tissues. Objective: The objective of the study was to gain insight into the downstream consequences of abnormal stimulatory G protein signaling in human epithelial tissues. Patients and Design: We assessed transcription of GNAS and Gsα-stimulated activation of the cystic fibrosis transmembrane conductance regulator (CFTR) in AHO patients, compared with normal controls and patients with cystic fibrosis. Main Outcome Measures: Relative expression of Gsα transcripts from each parental GNAS allele and cAMP measurements from nasal epithelial cells were compared among normal controls and AHO patients. In vivo measurements of CFTR function, pulmonary function, and pancreatic function were assessed in AHO patients. Results: GNAS was expressed equally from each allele in normals and two of five AHO patients. cAMP generation was significantly reduced in nasal respiratory epithelial cells from AHO patients, compared with normal controls (0.4 vs. 0.6, P = 0.0008). Activation of CFTR in vivo in nasal (P = 0.0065) and sweat gland epithelia (P = 0.01) of AHO patients was significantly reduced from normal. In three patients, the reduction in activity was comparable with patients with cystic fibrosis due to mutations in CFTR. Yet no AHO patients had pulmonary or pancreatic disease consistent with cystic fibrosis. Conclusions: In humans, haploinsufficiency of GNAS causes a significant reduction in the activation of the downstream target, CFTR, in vivo.

Mutation in the Gene Encoding the Stimulatory G Protein of Adenylate Cyclase in Albright's Hereditary Osteodystrophy

1990 ◽  
Vol 322 (20) ◽  
pp. 1412-1419 ◽  
Author(s):  
Jennifer L. Patten ◽  
Donald R. Johns ◽  
David Valle ◽  
Charles Eil ◽  
Philip A. Gruppuso ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
G Protein ◽  
Gene Encoding ◽  
Albright’S Hereditary Osteodystrophy ◽  
Stimulatory G Protein ◽  
Albright's Hereditary Osteodystrophy

scholarly journals G Proteins and GPCRs in C. elegans Development: A Story of Mutual Infidelity

2018 ◽  
Vol 6 (4) ◽  
pp. 28 ◽  
Author(s):  
Daniel Matúš ◽  
Simone Prömel
Keyword(s):  
Signaling Pathways ◽  
G Protein ◽  
G Proteins ◽  
Cell Polarity ◽  
Protein Activity ◽  
Independent Manner ◽  
C Elegans ◽  
Downstream Effectors ◽  
Complex Signaling ◽  
G Protein Coupled

Many vital processes during C. elegans development, especially the establishment and maintenance of cell polarity in embryogenesis, are controlled by complex signaling pathways. G protein-coupled receptors (GPCRs), such as the four Frizzled family Wnt receptors, are linchpins in regulating and orchestrating several of these mechanisms. However, despite being GPCRs, which usually couple to G proteins, these receptors do not seem to activate classical heterotrimeric G protein-mediated signaling cascades. The view on signaling during embryogenesis is further complicated by the fact that heterotrimeric G proteins do play essential roles in cell polarity during embryogenesis, but their activity is modulated in a predominantly GPCR-independent manner via G protein regulators such as GEFs GAPs and GDIs. Further, the triggered downstream effectors are not typical. Only very few GPCR-dependent and G protein-mediated signaling pathways have been unambiguously defined in this context. This unusual and highly intriguing concept of separating GPCR function and G-protein activity, which is not restricted to embryogenesis in C. elegans but can also be found in other organisms, allows for essential and multi-faceted ways of regulating cellular communication and response. Although its relevance cannot be debated, its impact is still poorly discussed, and C. elegans is an ideal model to understand the underlying principles.

scholarly journals Mutations in a gene encoding the alpha subunit of a Saccharomyces cerevisiae G protein indicate a role in mating pheromone signaling.

1988 ◽  
Vol 8 (6) ◽  
pp. 2484-2493 ◽  
Author(s):  
K Y Jahng ◽  
J Ferguson ◽  
S I Reed
Keyword(s):  
Saccharomyces Cerevisiae ◽  
G Protein ◽  
Genomic Library ◽  
Negative Impact ◽  
Receptor Gene ◽  
Temperature Sensitive ◽  
Specific Cell ◽  
Protein Activity ◽  
Mating Pheromone ◽  
Pheromone Receptor

Mutations which allowed conjugation by Saccharomyces cerevisiae cells lacking a mating pheromone receptor gene were selected. One of the genes defined by such mutations was isolated from a yeast genomic library by complementation of a temperature-sensitive mutation and is identical to the gene GPA1 (also known as SCG1), recently shown to be highly homologous to genes encoding the alpha subunits of mammalian G proteins. Physiological analysis of temperature-sensitive gpa1 mutations suggests that the encoded G protein is involved in signaling in response to mating pheromones. Mutational disruption of G-protein activity causes cell-cycle arrest in G1, deposition of mating-specific cell surface agglutinins, and induction of pheromone-specific mRNAs, all of which are responses to pheromone in wild-type cells. In addition, mutants can conjugate without the benefit of mating pheromone or pheromone receptor. A model is presented where the activated G protein has a negative impact on a constitutive signal which normally keeps the pheromone response repressed.

scholarly journals Exocytosis in mast cells by basic secretagogues: evidence for direct activation of GTP-binding proteins.

1990 ◽  
Vol 111 (3) ◽  
pp. 909-917 ◽  
Author(s):  
M Aridor ◽  
L M Traub ◽  
R Sagi-Eisenberg
Keyword(s):  
Mast Cells ◽  
G Protein ◽  
G Proteins ◽  
Independent Manner ◽  
Histamine Secretion ◽  
Free System ◽  
Stimulatory G Protein ◽  
A Cell ◽  
Secretion Inhibition ◽  
Gamma S

Histamine release induced by the introduction of a nonhydrolyzable analogue of GTP, GTP-gamma-S, into ATP-permeabilized mast cells, is associated with phosphoinositide breakdown, as evidenced by the production of phosphatidic acid (PA) in a neomycin-sensitive process. The dependency of both PA formation and histamine secretion on GTP-gamma-S concentrations is bell shaped. Whereas concentrations of up to 0.1 mM GTP-gamma-S stimulate both processes, at higher concentrations the cells' responsiveness is inhibited. At a concentration of 1 mM, GTP-gamma-S self-inhibits both PA formation and histamine secretion. Inhibition of secretion can, however, be overcome by the basic secretagogues compound 48/80 and mastoparan that in suboptimal doses synergize with 1 mM GTP-gamma-S to potentiate secretion. Secretion under these conditions is not accompanied by PA formation and is resistant both to depletion of Ca2+ from internal stores and to pertussis toxin (PtX) treatment. In addition, 48/80, like mastoparan, is capable of directly stimulating the GTPase activity of G-proteins in a cell-free system. Together, our results are consistent with a model in which the continuous activation of a phosphoinositide-hydrolyzing phospholipase C (PLC) by a stimulatory G-protein suffices to trigger histamine secretion. Basic secretagogues of mast cells, such as compound 48/80 and mastoparan, are capable of inducing secretion in a mechanism that bypasses PLC by directly activating a G-protein that is presumably located downstream from PLC (GE). Thereby, these secretagogues induce histamine secretion in a receptor-independent manner.

Sign in / Sign up

Export Citation Format

Share Document