Adenylate Cyclase (adenylyl cyclase)

2012 ◽  
Keyword(s):  
Adenylate Cyclase ◽  
Adenylyl Cyclase

scholarly journals Retargeting from the CR3 to the LFA-1 receptor uncovers the adenylyl cyclase enzyme–translocating segment of Bordetella adenylate cyclase toxin

2020 ◽  
Vol 295 (28) ◽  
pp. 9349-9365
Author(s):  
Jiri Masin ◽  
Adriana Osickova ◽  
David Jurnecka ◽  
Nela Klimova ◽  
Humaira Khaliq ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Adenylate Cyclase ◽  
Adenylyl Cyclase ◽  
Specific Capacity ◽  
Target Cells ◽  
Jurkat T Cells ◽  
Membrane Interaction ◽  
The Family ◽  
Adenylate Cyclase Toxin ◽  
Complement Receptor 3

The Bordetella adenylate cyclase toxin-hemolysin (CyaA) and the α-hemolysin (HlyA) of Escherichia coli belong to the family of cytolytic pore-forming Repeats in ToXin (RTX) cytotoxins. HlyA preferentially binds the αLβ2 integrin LFA-1 (CD11a/CD18) of leukocytes and can promiscuously bind and also permeabilize many other cells. CyaA bears an N-terminal adenylyl cyclase (AC) domain linked to a pore-forming RTX cytolysin (Hly) moiety, binds the complement receptor 3 (CR3, αMβ2, CD11b/CD18, or Mac-1) of myeloid phagocytes, penetrates their plasma membrane, and delivers the AC enzyme into the cytosol. We constructed a set of CyaA/HlyA chimeras and show that the CyaC-acylated segment and the CR3-binding RTX domain of CyaA can be functionally replaced by the HlyC-acylated segment and the much shorter RTX domain of HlyA. Instead of binding CR3, a CyaA1-710/HlyA411-1024 chimera bound the LFA-1 receptor and effectively delivered AC into Jurkat T cells. At high chimera concentrations (25 nm), the interaction with LFA-1 was not required for CyaA1-710/HlyA411-1024 binding to CHO cells. However, interaction with the LFA-1 receptor strongly enhanced the specific capacity of the bound CyaA1-710/HlyA411-1024 chimera to penetrate cells and deliver the AC enzyme into their cytosol. Hence, interaction of the acylated segment and/or the RTX domain of HlyA with LFA-1 promoted a productive membrane interaction of the chimera. These results help delimit residues 400–710 of CyaA as an “AC translocon” sufficient for translocation of the AC polypeptide across the plasma membrane of target cells.

scholarly journals Absence of pituitary adenylate cyclase-activating polypeptide-stimulated transcription of the human glycoprotein alpha-subunit gene in LbetaT2 gonadotrophs reveals disrupted cAMP-mediated gene transcription

2003 ◽  
Vol 31 (2) ◽  
pp. 263-278 ◽  
Author(s):  
RC Fowkes ◽  
KK Sidhu ◽  
JK Sosabowski ◽  
P King ◽  
JM Burrin
Keyword(s):  
Adenylate Cyclase ◽  
Adenylyl Cyclase ◽  
Radioligand Binding ◽  
Alpha Subunit ◽  
Regulatory Subunit ◽  
Pituitary Cells ◽  
Hormone Regulation ◽  
Glycoprotein Hormone ◽  
Altered Expression ◽  
Pituitary Adenylate Cyclase

Hormone regulation of anterior pituitary expression of the common glycoprotein hormone alpha-subunit (alphaGSU) is mediated by multiple response elements residing in the first -435 bp of the human promoter. In rat pituitary cells and mouse alphaT3-1 precursor gonadotrophs, the human alphaGSU promoter is strongly responsive to activators of the adenylyl cyclase/cAMP pathway, such as the hypothalamic releasing hormone, pituitary adenylate cyclase-activating polypeptide (PACAP) and forskolin (an adenylyl cyclase activator). However, the role of PACAP and cAMP in regulating alphaGSU transcription in the more differentiated LbetaT2 gonadotroph is unclear. Here, we investigate the regulation of the human alphaGSU promoter by PACAP and forskolin in LbetaT2 and alphaT3-1 gonadotrophs. PACAP failed to stimulate alphaGSU promoter activity or cAMP production in LbetaT2 cells, in marked contrast to alphaT3-1 cells. LbetaT2 gonadotrophs expressed extremely low levels of any PACAP type 1 receptors (PAC(1)-R) isoform by RT-PCR and lacked PAC(1)-R by radioligand binding. Forskolin stimulated the alphaGSU promoter in LbetaT2 cells, but by less than 30% of the response seen in alphaT3-1 gonadotrophs. This blunted cAMP transcriptional effect was not due to different levels of cAMP generation, or altered expression of the cAMP target proteins CREB, Akt, CBP or ICER. However, only LbetaT2 cells showed detectable expression of the protein kinase A type IIalpha regulatory subunit. Binding of activating transcription factor-2 and phosphorylated CREB to the consensus CRE was observed in both LbetaT2 and alphaT3-1 gonadotrophs, yet forskolin failed to stimulate either CRE- or CREB-mediated transcription in LbetaT2 cells. Collectively, these data demonstrate the lack of functional PACAP receptors in LbetaT2 gonadotrophs, and a pronounced attenuation in the responsiveness of this differentiated gonadotroph cell line to cAMP stimulus.

A LOV-domain-mediated blue-light-activated adenylate (adenylyl) cyclase from the cyanobacterium Microcoleus chthonoplastes PCC 7420

2013 ◽  
Vol 455 (3) ◽  
pp. 359-365 ◽  
Author(s):  
Sarah Raffelberg ◽  
Linzhu Wang ◽  
Shiqiang Gao ◽  
Aba Losi ◽  
Wolfgang Gärtner ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Adenylyl Cyclase ◽  
Blue Light ◽  
Lov Domain ◽  
E Coli ◽  
Microcoleus Chthonoplastes

We describe the first adenylate cyclase with a LOV domain. The protein, which we name mPAC, originates from a cyanobacterium but is photoactivated in vertebrate cells and could be purified and functionally characterized after expression in E. coli.

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Stimulates Adenylyl Cyclase and Phospholipase C Activity in Rat Cerebellar Neuroblasts

2002 ◽  
Vol 65 (3) ◽  
pp. 1318-1324 ◽  
Author(s):  
Magali Basille ◽  
Bruno J. Gonzalez ◽  
Laurence Desrues ◽  
Myriam Demas ◽  
Alain Fournier ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Adenylyl Cyclase ◽  
Phospholipase C ◽  
Pituitary Adenylate Cyclase

scholarly journals Interactions of ovarian steroids with pituitary adenylate cyclase-activating polypeptide and GnRH in anterior pituitary cells

1999 ◽  
pp. 207-214 ◽  
Author(s):  
O Ortmann ◽  
W Asmus ◽  
K Diedrich ◽  
KD Schulz ◽  
G Emons
Keyword(s):  
Adenylate Cyclase ◽  
Adenylyl Cyclase ◽  
Anterior Pituitary ◽  
Pituitary Cells ◽  
Camp Production ◽  
Estradiol Treatment ◽  
Ovarian Steroids ◽  
Anterior Pituitary Cells ◽  
Pituitary Adenylate Cyclase ◽  
Lh Secretion

Pituitary adenylate cyclase-activating polypeptide (PACAP) releases LH and FSH from anterior pituitary cells. Although this effect is relatively weak, it has a strong sensitizing action on GnRH-induced gonadotropin secretion. Here we investigated the possibility that ovarian steroids, which are well-known modulators of LH secretion, interact with PACAP and GnRH in pituitary gonadotrophs. Rat pituitary cells were treated for 48 h with vehicle, 1 nmol/l estradiol, 1 nmol/l estradiol + 100 nmol/l progesterone or 48 h with 1 nmol/l estradiol and 4 h with 100 nmol/l progesterone. The cells were stimulated for 3 h with 1 nmol/l GnRH or 100 nmol/l PACAP. Estradiol treatment alone enhanced basal as well as GnRH- or PACAP-stimulated LH secretion. LH release was facilitated by additional short-term progesterone treatment. Long-term treatment with estradiol and progesterone led to reduced LH responses to GnRH and PACAP. Neither treatment paradigms affected cAMP production. However, estradiol treatment led to enhanced cAMP accumulation in quiescent or GnRH-stimulated cells. PACAP-induced increases of cAMP production were inhibited by estradiol treatment. After 7-h preincubation with 10 nmol/l PACAP, cells responded with enhanced LH secretion to GnRH stimulation. When steroid pretreatment was performed the responsiveness of gonadotrophs to low concentrations of GnRH was still increased. In contrast, at high concentrations of GnRH the sensitizing action of PACAP on agonist-induced LH secretion was lost in steroid-treated cells. There were no significant differences between the steroid treatment paradigms. It is concluded that estradiol but not progesterone acts as a modulator of adenylyl cyclase in gonadotrophs. The stimulatory effect of estradiol is thought to be involved in its sensitizing action on agonist-induced LH secretion. The inhibitory effect of estradiol on PACAP-stimulated adenylyl cyclase activities seems to be responsible for the loss of its action to sensitize LH secretory responses to GnRH.

Cytochemical Evidence for Presynatic β-Adrenergic Regulation of Secretion in the Developing Rat Submandibular Gland

1977 ◽  
Vol 35 ◽  
pp. 430-431
Author(s):  
L.S. Cutler
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Submandibular Gland ◽  
Neonatal Rat ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Parotid Glands ◽  
Adrenergic Agonist ◽  
Rat Submandibular Gland

Many studies previously have shown that the B-adrenergic agonist isoproterenol and the a-adrenergic agonist norepinephrine will stimulate secretion by the adult rat submandibular (SMG) and parotid glands. Recent data from several laboratories indicates that adrenergic agonists bind to specific receptors on the secretory cell surface and stimulate membrane associated adenylate cyclase activity which generates cyclic AMP. The production of cyclic AMP apparently initiates a cascade of events which culminates in exocytosis. During recent studies in our laboratory it was observed that the adenylate cyclase activity in plasma membrane fractions derived from the prenatal and early neonatal rat submandibular gland was retractile to stimulation by isoproterenol but was stimulated by norepinephrine. In addition, in vitro secretion studies indicated that these prenatal and neonatal glands would not secrete peroxidase in response to isoproterenol but would secrete in response to norepinephrine. In contrast to these in vitro observations, it has been shown that the injection of isoproterenol into the living newborn rat results in secretion of peroxidase by the SMG (1).

Opiate-Inhibited Adenylate Cyclase in Mammalian Brain Membranes

1986 ◽  
Author(s):  
Steven R. Childers ◽  
Peter Nijssen ◽  
Pauline Nadeau ◽  
Page Buckhannan ◽  
Phi-Van Le ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Mammalian Brain ◽  
Brain Membranes
Sign in / Sign up

Export Citation Format

Share Document