Differential activation of adenylyl cyclase by protein kinase C isoenzymes

Kawabe, Jun‐ichi; Iwami, Gensho; Ebina, Toshiaki; Ohno, Shigeo; Katada, Toshiaki; Ueda, Yoshihiko; Homcy, Charles J.; Ishikawa, Yoshihiro

doi:10.1016/s0021-9258(19)89424-3

Cited by 193 publications

(8 citation statements)

References 38 publications

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“…Recent work by Lai et al (37) demonstrated that the ACVI isoform is directly phosphorylated and inhibited by PKCδ and PKC , which are known to be expressed in the heart. ACV, alternatively, is stimulated by PKCR and PKCζ (38). It appears that PKA phosphorylates and inhibits both ACV and ACVI (39,40).…”

Section: Discussionmentioning

confidence: 99%

Altering the Receptor−Effector Ratio by Transgenic Overexpression of Type V Adenylyl Cyclase: Enhanced Basal Catalytic Activity and Function without Increased Cardiomyocyte β-Adrenergic Signalling

et al. 1999

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The limiting element in beta-adrenergic receptor (betaAR)-G(s)-adenylyl cyclase (AC) signal transduction in the cardiomyocyte is not known, but it has been proposed that the level of adenylyl cyclase expression constrains betaAR signaling. To alter the above equilibrium, type V AC was overexpressed in a myocyte-specific manner in the hearts of transgenic mice using the alpha-myosin heavy chain promoter. Expression of type V AC was approximately 75% over endogenous levels as quantitated by [(3)H]forskolin binding. Functional activity of the transgene product was evident in cardiac membrane AC studies, where basal (45 +/- 11 vs 19 +/- 5 pmol min(-)(1) mg(-)(1)) and forskolin+Mn(2+) (695 +/- 104 vs 386 +/- 34 pmol min(-)(1) mg(-)(1)) stimulated activities were increased compared to activities in nontransgenic (NTG) littermates. However, while isoproterenol stimulated activities were higher (74 +/- 12 vs 46 +/- 9.8 pmol min(-)(1) mg(-)(1)), the fold stimulation over basal was not increased in ACV overexpressors compared to NTG (line 14.3 = 2.29 +/- 0.44-fold, line 15.1 = 1.70 +/- 0.1-fold, NTG = 2.62 +/- 0.18-fold). Similarly, in whole cell patch-clamp studies, betaAR-mediated opening of L-type Ca(2+) channels was not found to be enhanced in transgenic ACV myocytes (225 +/- 15 vs 216 +/- 10% of basal currents). Basal and isoproterenol stimulated PKA activities were elevated in the ACV mice compared to NTG, but again the extent of stimulation over basal was not enhanced. Phosphorylated phospholamban was approximately 2-fold greater in myocytes from ACV hearts compared to NTG, indicating that distal elements of the contractile cascade are activated by AC overexpression. ACV mice displayed increased heart rates and fractional shortening as assessed by echocardiography. However, in vivo hemodynamic studies revealed that heart rate and contractility responses to agonist infusion were not enhanced in ACV mice compared to NTG. We conclude that at native stoichiometries, the levels of adenylyl cyclase influence basal activities and cardiac function, but do not constrain betaAR signaling in the cardiomyocyte.

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Section: Discussionmentioning

confidence: 99%

Altering the Receptor−Effector Ratio by Transgenic Overexpression of Type V Adenylyl Cyclase: Enhanced Basal Catalytic Activity and Function without Increased Cardiomyocyte β-Adrenergic Signalling

et al. 1999

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“…The importance of similar regulation in vivo is, however, suggested by the fact that individual ACs are selective for specific PKC isoforms. For instance, work by Kawabe and colleagues (208,209) revealed preferential stimulation of AC5 by PKC-over PKC-␣. In contrast, AC6 exhibited reduced activity following activation of numerous PKC isoforms (␤, ␦, and ) in osteoblastic cells (76).…”

Section: Pkcmentioning

confidence: 99%

Organization and Ca²⁺Regulation of Adenylyl Cyclases in cAMP Microdomains

Willoughby

Cooper²

2007

Physiological Reviews

405

361

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The adenylyl cyclases are variously regulated by G protein subunits, a number of serine/threonine and tyrosine protein kinases, and Ca(2+). In some physiological situations, this regulation can be readily incorporated into a hormonal cascade, controlling processes such as cardiac contractility or neurotransmitter release. However, the significance of some modes of regulation is obscure and is likely only to be apparent in explicit cellular contexts (or stages of the cell cycle). The regulation of many of the ACs by the ubiquitous second messenger Ca(2+) provides an overarching mechanism for integrating the activities of these two major signaling systems. Elaborate devices have been evolved to ensure that this interaction occurs, to guarantee the fidelity of the interaction, and to insulate the microenvironment in which it occurs. Subcellular targeting, as well as a variety of scaffolding devices, is used to promote interaction of the ACs with specific signaling proteins and regulatory factors to generate privileged domains for cAMP signaling. A direct consequence of this organization is that cAMP will exhibit distinct kinetics in discrete cellular domains. A variety of means are now available to study cAMP in these domains and to dissect their components in real time in live cells. These topics are explored within the present review.

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“…15 The mammalian type V adenylate cyclase is phosphorylated by protein kinase C and protein kinase A, and the phosphorylation regulates the activity of the enzyme. 16,17 In budding yeast Saccharomyces cerevisiae the adenylate cyclase is activated by Ras, which is a small GTP-binding protein. 18,19 We have isolated anenylate cyclase genes from cyanobacteria and characterized their molecular properties.…”

Section: Introductionmentioning

confidence: 99%

Photoresponsive cAMP signal transduction in cyanobacteria

Ohmori

Okamoto

2004

Photochem Photobiol Sci

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The molecular mechanism of cAMP-mediated signal transduction from light reception to the physiological response via regulation of gene expression in cyanobacteria is described based on our recent works. Cyanobacteria are known as the organisms that acquired oxygen-evolving, higher plant type photosynthesis. We have found that the cellular cAMP level in the filamentous cyanobacteria Anabaena was oppositely regulated by red and far-red light, i.e., decreasing and increasing, respectively, suggesting that a phytochrome-like red/far-red photoreversible pigment regulates the activity of a certain adenylate cyclase. On the other hand, in the unicellular cyanobacterium Synechocystis cellular cAMP content was increased by blue light irradiation, which led to stimulation of cell motility. The cAMP signaling pathway is known to play an important role in the regulation of various biological activities by altering enzyme activities or controlling gene expression levels in both prokaryotes and eukaryotes. We have isolated genes for adenylate cyclases and cAMP receptor proteins and characterized their molecular properties. Disruption of these genes resulted in the loss of cell motility. It is concluded that the light signal was transmitted by cAMP signal cascade in cyanobacteria.

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Differential activation of adenylyl cyclase by protein kinase C isoenzymes

Cited by 193 publications

References 38 publications

Altering the Receptor−Effector Ratio by Transgenic Overexpression of Type V Adenylyl Cyclase: Enhanced Basal Catalytic Activity and Function without Increased Cardiomyocyte β-Adrenergic Signalling

Altering the Receptor−Effector Ratio by Transgenic Overexpression of Type V Adenylyl Cyclase: Enhanced Basal Catalytic Activity and Function without Increased Cardiomyocyte β-Adrenergic Signalling

Organization and Ca²⁺Regulation of Adenylyl Cyclases in cAMP Microdomains

Photoresponsive cAMP signal transduction in cyanobacteria

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Differential activation of adenylyl cyclase by protein kinase C isoenzymes

Cited by 193 publications

References 38 publications

Altering the Receptor−Effector Ratio by Transgenic Overexpression of Type V Adenylyl Cyclase: Enhanced Basal Catalytic Activity and Function without Increased Cardiomyocyte β-Adrenergic Signalling

Altering the Receptor−Effector Ratio by Transgenic Overexpression of Type V Adenylyl Cyclase: Enhanced Basal Catalytic Activity and Function without Increased Cardiomyocyte β-Adrenergic Signalling

Organization and Ca2+Regulation of Adenylyl Cyclases in cAMP Microdomains

Photoresponsive cAMP signal transduction in cyanobacteria

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Organization and Ca²⁺Regulation of Adenylyl Cyclases in cAMP Microdomains