Sequence similarity of phospholipase A2 activating protein and the G protein β-subunits: a new concept of effector protein activation in signal transduction?

1993 ◽  
Vol 18 (8) ◽  
pp. 292-293 ◽  
Author(s):  
Manuel C. Peitsch ◽  
Christoph Borner ◽  
Jürg Tschopp
Keyword(s):  
Signal Transduction ◽  
Phospholipase A2 ◽  
G Protein ◽  
Sequence Similarity ◽  
Effector Protein ◽  
Protein Activation

scholarly journals Mechanism of cAMP-induced Ca2+ influx in Dictyostelium: role of phospholipase A2

1997 ◽  
Vol 327 (1) ◽  
pp. 233-238 ◽  
Author(s):  
Ralph SCHALOSKE ◽  
Dieter MALCHOW
Keyword(s):  
Phospholipase A2 ◽  
G Protein ◽  
Sequence Similarity ◽  
Similar Extent ◽  
Kinase C ◽  
Maximal Activation ◽  
Receptor Concentration ◽  
Camp Receptor ◽  
Dependent Pathway

cAMP-induced Ca2+ influx in Dictyostelium follows two pathways: a G-protein-dependent pathway where influx is reduced by 50–70% in Gα2 and Gβ-negative strains and a heterotrimeric G-protein-independent pathway. Using a pharmacological approach, we found that phospholipase A2 (PLA2) is the target of both pathways. The products of PLA2 activity, arachidonic acid (AA) and palmitic acid, induced Ca2+ influx to a similar extent as cAMP. Half-maximal activation occurred at 3 μM AA and saturation at 10 μM AA. The response to AA was quantitatively similar throughout early differentiation and thusindependent of cAMP-receptor concentration. Synergy experiments revealed that cAMP and AA acted through identical pathways. The PLA2-activating peptide, a peptide with sequence similarity to the G-protein β-subunit, activated Ca2+ influx. The G-protein-independent pathway was sensitive to genistein but not to blockers of protein kinase C and other kinases, suggesting that tyrosine kinase may directly or indirectly activate PLA2 in this case.

Acupuncture Upregulates G Protein Coupled Activity in Samp8 Mice

2017 ◽  
Vol 35 (4) ◽  
pp. 289-296 ◽  
Author(s):  
Benhua Luo ◽  
Lan Zhao ◽  
Xuezhu Zhang ◽  
Bohong Kan ◽  
Yunhe Liu ◽  
...  
Keyword(s):  
Signal Transduction ◽  
G Protein ◽  
Cognitive Deficits ◽  
Control Group ◽  
Protein Activity ◽  
Western Blots ◽  
Protein Activation ◽  
Activation Rate ◽  
Cellular Signal ◽  
Samp8 Mice

Background Transmembrane and intracellular signal transduction of G protein is closely related to the pathophysiology of Alzheimer's disease (AD). Objective To explore the effects of Sanjiao acupuncture on G protein signal transduction pathways in the pathogenesis of AD. Methods 36 senescence-accelerated (SAM) prone 8 mice were divided into three groups that remained untreated (SAMP8, n=12) or received Sanjiao acupuncture (SAMP8+SA, n=12) or control acupuncture (SAMP8+CA, n=12). An additional control group of SAM resistant 1 mice was included (SAMR1 group, n=12). Morris water maze tests were used to investigate learning and memory abilities. Immunoprecipitation and Western blotting were used to study expression of G protein subunits and their activities in the cortex/hippocampus. Results Behavioural analysis showed that acupuncture attenuated the severe cognitive deficits observed in untreated/CA-treated SAMP8 mice. The findings of the G protein activation assays via immunoprecipitation and Western blots were that the physiologically coupled activation rate (PCAR) and maximal coupled activation rate (MCAR) of Gαs and Gαi were decreased in the cortex of SAMP8 vs SAMR1 mice. Sanjiao acupuncture induced an upregulation in the PCAR of Gαs and Gαi. In the hippocampus of untreated SAMP8 mice, the PCAR of Gαs and MCAR of both Gαs and Gαi declined, and Sanjiao acupuncture was associated with an upregulation in the MCAR of Gαs and Gαi. There were no significant differences in Gαs and Gαi expression between the groups. Conclusions Sanjiao acupuncture attenuates cognitive deficits in a mouse model of AD via upregulation of G protein activity and stabilisation of the cellular signal.

scholarly journals Label-Free Investigations on the G Protein Dependent Signaling Pathways of Histamine Receptors

2021 ◽  
Vol 22 (18) ◽  
pp. 9739 ◽  
Author(s):  
Ulla Seibel-Ehlert ◽  
Nicole Plank ◽  
Asuka Inoue ◽  
Guenther Bernhardt ◽  
Andrea Strasser
Keyword(s):  
Signal Transduction ◽  
G Protein ◽  
Drug Targets ◽  
Physiological Role ◽  
Histamine Receptors ◽  
Label Free ◽  
Knock Out ◽  
Protein Activation ◽  
Hek Cells ◽  
Molecular Events

G protein activation represents an early key event in the complex GPCR signal transduction process and is usually studied by label-dependent methods targeting specific molecular events. However, the constrained environment of such “invasive” techniques could interfere with biological processes. Although histamine receptors (HRs) represent (evolving) drug targets, their signal transduction is not fully understood. To address this issue, we established a non-invasive dynamic mass redistribution (DMR) assay for the human H1–4Rs expressed in HEK cells, showing excellent signal-to-background ratios above 100 for histamine (HIS) and higher than 24 for inverse agonists with pEC50 values consistent with literature. Taking advantage of the integrative nature of the DMR assay, the involvement of endogenous Gαq/11, Gαs, Gα12/13 and Gβγ proteins was explored, pursuing a two-pronged approach, namely that of classical pharmacology (G protein modulators) and that of molecular biology (Gα knock-out HEK cells). We showed that signal transduction of hH1–4Rs occurred mainly, but not exclusively, via their canonical Gα proteins. For example, in addition to Gαi/o, the Gαq/11 protein was proven to contribute to the DMR response of hH3,4Rs. Moreover, the Gα12/13 was identified to be involved in the hH2R mediated signaling pathway. These results are considered as a basis for future investigations on the (patho)physiological role and the pharmacological potential of H1–4Rs.

scholarly journals DAPLE and MPDZ bind to each other and cooperate to promote apical cell constriction

2019 ◽  
Vol 30 (16) ◽  
pp. 1900-1910 ◽  
Author(s):  
Arthur Marivin ◽  
Mikel Garcia-Marcos
Keyword(s):  
G Protein ◽  
Cultured Cells ◽  
Apical Cell ◽  
Cell Junctions ◽  
Binding Motif ◽  
Apical Constriction ◽  
Protein Activation ◽  
Neuroepithelial Cells ◽  
Two Factors ◽  
Apical Junctions

Dishevelled-Associating Protein with a high frequency of LEucines (DAPLE) belongs to a group of unconventional activators of heterotrimeric G-proteins that are cytoplasmic factors rather than membrane proteins of the G-protein–coupled receptor superfamily. During neurulation, DAPLE localizes to apical junctions of neuroepithelial cells and promotes apical cell constriction via G-protein activation. While junctional localization of DAPLE is necessary for this function, the factors it associates with at apical junctions or how they contribute to DAPLE-mediated apical constriction are unknown. MPDZ is a multi-PDZ (PSD95/DLG1/ZO-1) domain scaffold present at apical cell junctions whose mutation in humans is linked to nonsyndromic congenital hydrocephalus (NSCH). DAPLE contains a PDZ-binding motif (PBM) and is also mutated in human NSCH, so we investigated the functional relationship between both proteins. DAPLE colocalized with MPDZ at apical cell junctions and bound directly to the PDZ3 domain of MPDZ via its PBM. Much like DAPLE, MPDZ is induced during neurulation in Xenopus and is required for apical constriction of neuroepithelial cells and subsequent neural plate bending. MPDZ depletion also blunted DAPLE-­mediated apical constriction of cultured cells. These results show that DAPLE and MPDZ, two factors genetically linked to NSCH, function as cooperative partners at apical junctions and are required for proper tissue remodeling during early stages of neurodevelopment.

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