Direct Effects of Cutaneous Neuropeptides on Adenylyl Cyclase Activity and Proliferation in a Keratinocyte Cell Line: Stimulation of Cyclic AMP Formation by CGRP and VIP/PHM, and Inhibition by NPY Through G Protein-Coupled Receptors

1993 ◽  
Vol 101 (5) ◽  
pp. 646-651 ◽  
Author(s):  
Kenzo Takahashi ◽  
Shigetada Nakanishi ◽  
Sadao Imamura
Keyword(s):  
Cyclic Amp ◽  
Adenylyl Cyclase ◽  
Cell Line ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Direct Effects ◽  
Adenylyl Cyclase Activity ◽  
Keratinocyte Cell ◽  
G Protein Coupled ◽  
Stimulation Of

Regulation of adenylyl cyclase in polarized renal epithelial cells by G protein-coupled receptors

1997 ◽  
Vol 273 (6) ◽  
pp. F883-F891 ◽  
Author(s):  
Mark D. Okusa ◽  
Liping Huang ◽  
Akemi Momose-Hotokezaka ◽  
Long P. Huynh ◽  
Amy J. Mangrum
Keyword(s):  
Epithelial Cells ◽  
Adenylyl Cyclase ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Cyclase Activity ◽  
Camp Accumulation ◽  
Adenylyl Cyclase Activity ◽  
Renal Epithelial Cells ◽  
G Protein Coupled ◽  
Stimulation Of

We employed two guanine nucleotide binding protein (G protein)-coupled receptors known to be targeted to opposite domains in renal epithelial cells to test the hypothesis that the polarized receptor expression of receptors regulates the activity of the receptor’s effector molecule, adenylyl cyclase. We used LLC-PK1 cells stably transfected with cDNA encoding the α2B-adrenergic receptor (α2B-AR) or A1-adenosine receptor (A1-AdR). Immunohistochemistry and Western blot analysis confirmed the basolateral and apical expression of α2B-ARs and A1-AdRs, respectively. Adenylyl cyclase activity was assessed by measuring cAMP accumulation following the addition of forskolin (10 μM) in the presence of 3-isobutyl-1-methylxanthine to apical or basolateral chambers of confluent monolayers. A five- to sixfold increase in cAMP accumulation occurred following apical (or basolateral) stimulation of LLC-PK1 cells expressing apical (or basolateral) receptors in comparison to forskolin stimulation of corresponding domains of untransfected cells. We conclude 1) adenylyl cyclase activity is present at or near the apical and basolateral domains of LLC-PK1 cells, and 2) factors that regulate the polarized expression of inhibitory G protein-coupled receptors may also regulate local adenylyl cyclase activity.

Dexamethasone increases G alpha q-11 expression and hormone-stimulated phospholipase C activity in UMR-106-01 cells.

1997 ◽  
Vol 273 (3) ◽  
pp. E528 ◽  
Author(s):  
J Mitchell ◽  
A Bansal
Keyword(s):  
Adenylyl Cyclase ◽  
Phospholipase C ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Beta Subunits ◽  
Adenylyl Cyclase Activity ◽  
Protein Subunits ◽  
G Alpha Q ◽  
Umr 106 ◽  
G Protein Coupled

Glucocorticoids regulate responsiveness of many cells to hormones that bind to G protein-coupled receptors. We examined the effect of glucocorticoids on parathyroid hormone (PTH) activation of two G protein-activated signal transduction pathways, phospholipase C (PLC) and adenylyl cyclase, in osteosarcoma UMR-106-01 cells. Dexamethasone (100 nM) increased PTH-stimulated and NaF-stimulated PLC activity by > 100% over 4 days (223 +/- 8 and 293 +/- 8.2% of control after 4 days for PTH and NaF-stimulated activity, respectively). The increase in PTH-stimulated adenylyl cyclase response in the same cells was more modest (162 +/- 5.4 and 171 +/- 6.8% of control after 4 days for PTH and NaF-stimulated activity, respectively). PTH activation of PLC was blocked by antiserums to G alpha q-11 and activation of adenylyl cyclase by G alpha s antiserums. Quantification of these G protein subunits in control and dexamethasone-treated cells showed a 78% increase in G alpha q-11 (from 18.1 +/- 1.2 to 32.2 +/- 1.5 pmol/mg), whereas G alpha s was increased only 34% (from 6.2 +/- 0.5 to 8.2 +/- 0.3 pmol/mg) and G beta-subunits were increased 40% (from 54 +/- 2.3 to 75.2 +/- 3.8 pmol/mg). These results suggest that glucocorticoids are more potent regulators of PLC activity than adenylyl cyclase activity in UMR cells, and this is mediated, at least in part, by differential increases in G alpha q-11 proteins.

Clonal variation of adenylyl cyclase activity in a rat tumor cell line caused by change in G protein-catalytic unit interaction

1990 ◽  
Vol 144 (3) ◽  
pp. 448-456 ◽  
Author(s):  
Masahiro Kawabata ◽  
Hiroshi Yoshikura ◽  
Keizo Horio ◽  
Kenji Fujiwara ◽  
Aikichi Iwamoto
Keyword(s):  
Tumor Cell ◽  
Adenylyl Cyclase ◽  
Cell Line ◽  
G Protein ◽  
Tumor Cell Line ◽  
Cyclase Activity ◽  
Clonal Variation ◽  
Adenylyl Cyclase Activity ◽  
Catalytic Unit ◽  
Rat Tumor

scholarly journals The metalloprotease Kuzbanian (ADAM10) mediates the transactivation of EGF receptor by G protein–coupled receptors

2002 ◽  
Vol 158 (2) ◽  
pp. 221-226 ◽  
Author(s):  
Yibing Yan ◽  
Kyoko Shirakabe ◽  
Zena Werb
Keyword(s):  
Signaling Pathways ◽  
G Protein ◽  
Egf Receptor ◽  
Critical Role ◽  
G Protein Coupled Receptors ◽  
Heparin Binding ◽  
Egf Receptors ◽  
Gpcr Activation ◽  
G Protein Coupled ◽  
Stimulation Of

Communication between different signaling pathways enables cells to coordinate the responses to diverse environmental signals. Activation of the transmembrane growth factor precursors plays a critical role in this communication and often involves metalloprotease-mediated proteolysis. Stimulation of G protein–coupled receptors (GPCR) transactivates the EGF receptors (EGFRs), which occurs via a metalloprotease-dependent cleavage of heparin-binding EGF (HB-EGF). However, the metalloprotease mediating the transactivation remains elusive. We show that the integral membrane metalloprotease Kuzbanian (KUZ; ADAM10), which controls Notch signaling in Drosophila, stimulates GPCR transactivation of EGFR. Upon stimulation of the bombesin receptors, KUZ increases the docking and activation of adaptors Src homology 2 domain–containing protein and Gab1 on the EGFR, and activation of Ras and Erk. In contrast, transfection of a protease domain–deleted KUZ, or blocking endogenous KUZ by morpholino antisense oligonucleotides, suppresses the transactivation. The effect of KUZ on shedding of HB-EGF and consequent transactivation of the EGFR depends on its metalloprotease activity. GPCR activation enhances the association of KUZ and its substrate HB-EGF with tetraspanin CD9. Thus, KUZ regulates the relay between the GPCR and EGFR signaling pathways.

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