Signal recognition and integration by GS-stimulated adenylyl cyclases

Pieroni, Joseph P.; Jacobowitz, Ofer; Chen, Jianqiang; lyengar, Ravi

doi:10.1016/0959-4388(93)90127-k

Cited by 57 publications

(36 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is now well established that the different mammalian adenylyl cyclases have unique signal recognition capabilities (9,20). This allows the cAMP pathway to respond to a variety of G protein-coupled receptors (21) as well as receptor tyrosine kinases that stimulate protein kinase C activity.…”

Section: Discussionmentioning

confidence: 99%

Distinct Characteristics of the Basal Activities of Adenylyl Cyclases 2 and 6

Pieroni

Harry

Chen

et al. 1995

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Distinct Characteristics of the Basal Activities of Adenylyl Cyclases 2 and 6

Pieroni

Harry

Chen

et al. 1995

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…This is of particular physiological importance since adenylyl cyclase activity is regulated by a complex network of interacting pathways (for review, see Refs. [33][34][35][36][37]. For example, adenylyl cyclase isoforms present in S49 cells, Type VI and Type VII (29,38), are regulated by Ca 2ϩ , PKA, PKC, G␣ s , and G␣ i (28,38,39 and references therein).…”

Section: Discussionmentioning

confidence: 99%

A Key Role for Protein Kinase A in Homologous Desensitization of the β2-Adrenergic Receptor Pathway in S49 Lymphoma Cells

Post

Aguila-Buhain

Insel

1996

Journal of Biological Chemistry

View full text Add to dashboard Cite

Desensitization of receptor-mediated cellular responses is a complex process which can involve multiple pathways including: (a) receptor uncoupling from G protein, (b) sequestration of receptors away from the plasma membrane, and (c) downregulation of signaling proteins (1-4). It has been demonstrated that uncoupling of receptor and G protein occurs rapidly (within 10 min) in response to receptor activation and appears to involve receptor phosphorylation (5). In the case of the ␤ 2 -adrenergic receptor (␤ 2 -AR) 1 system, agonist-occupied receptors activate the stimulatory G protein, G s , which in turn promotes the production of cAMP by adenylyl cyclase. Increased cAMP levels activate the cAMP-dependent protein kinase (PKA) resulting in the phosphorylation of several proteins, including the ␤ 2 -AR and other receptors. In addition, agonist-occupied ␤ 2 -AR are phosphorylated by one or more isoforms of the ␤-adrenergic receptor kinase (␤-ARK, also termed G protein receptor kinase; GRK) resulting in the uncoupling of receptor and G s (6 -10). Therefore, both PKA and ␤-ARK can contribute to desensitization of the ␤ 2 -AR system. In contrast to the effect of ␤-ARK, PKA-mediated ␤ 2 -AR phosphorylation is most often associated with heterologous desensitization (that which is agonist nonspecific and therefore not dependent on ␤ 2 -AR occupancy), but is generally thought to be of little importance in homologous desensitization (agonistspecific and dependent on ␤ 2 -AR occupancy) (11-14). Therefore, while the ␤ 2 -AR can be phosphorylated by both PKA and ␤-ARK, most recent work has focused on the importance of ␤-ARK and related proteins (reviewed in Refs. 6 and 15-17) as mediators of homologous desensitization.The kin Ϫ S49 murine lymphoma cell lacks PKA activity and thus provides a unique system in which to study the relative importance of PKA in mediating various cellular responses. Importantly, both WT and kin Ϫ S49 cells express only the ␤ 2 -AR isoform and display similar profiles of ␤-AR agonistinduced desensitization of cAMP production and cell-surface ␤ 2 -AR loss (14, 18). The ability of the cell-permeable cAMP analog, 8-Br-cAMP, to mimic the effect of epinephrine in decreasing ␤-AR agonist-induced adenylyl cyclase activity in membranes prepared from treated cells suggest that the effect of PKA activation is not dependent on the presence of agonist (11). These results suggest that PKA is not involved in homologous desensitization of the ␤ 2 -AR.In the current studies, we have used a [ 3 H]forskolin binding assay to define more precisely the role of PKA in desensitizing the ␤ 2 -AR system in intact S49 cells. Since high-affinity forskolin interaction with adenylyl cyclase requires the activation of G␣ s , the amount of [ 3 H]forskolin associated with cells can be used as an index of G␣ s -adenylyl cyclase interaction (19 -21). This assay, therefore, both provides a direct means of assessing hormone-stimulated G␣ s -adenylyl cyclase interaction in intact cells that is independent of second messenger accumulation...

show abstract

“…For example, Sugita et al (1997) showed that activation of PKC by phorbol esters specifically attenuated aspects of the 5-HT activation of the cAMP/PKA cascade. Previous studies have demonstrated that PKC interacts with a cAMP/PKA cascade at the level of AC by increasing its activity and consequently the level of cAMP (for review, see Pieroni et al 1993;Cooper et al 1995). PKC can also interact with the PKA cascade at the level of the receptor.…”

Section: Cross-talk Between 5-ht Receptors In Aplysiamentioning

confidence: 99%

Multiple Serotonergic Mechanisms Contributing to Sensitization in Aplysia: Evidence of Diverse Serotonin Receptor Subtypes

Barbas¹,

DesGroseillers²,

Castellucci³

et al. 2003

Learn. Mem.

105

View full text Add to dashboard Cite

The neurotransmitter serotonin (5-HT) plays an important role in memory encoding in Aplysia. Early evidence showed that during sensitization, 5-HT activates a cyclic AMP-protein kinase A (cAMP-PKA)-dependent pathway within specific sensory neurons (SNs), which increases their excitability and facilitates synaptic transmission onto their follower motor neurons (MNs). However, recent data suggest that serotonergic modulation during sensitization is more complex and diverse. The neuronal circuits mediating defensive reflexes contain a number of interneurons that respond to 5-HT in ways opposite to those of the SNs, showing a decrease in excitability and/or synaptic depression. Moreover, in addition to acting through a cAMP-PKA pathway within SNs, 5-HT is also capable of activating a variety of other protein kinases such as protein kinase C, extracellular signal-regulated kinases, and tyrosine kinases. This diversity of 5-HT responses during sensitization suggests the presence of multiple 5-HT receptor subtypes within the Aplysia central nervous system. Four 5-HT receptors have been cloned and characterized to date. Although several others probably remain to be characterized in molecular terms, especially the Gs-coupled 5-HT receptor capable of activating cAMP-PKA pathways, the multiplicity of serotonergic mechanisms recruited into action during learning in Aplysia can now be addressed from a molecular point of view.The marine mollusk Aplysia has proven to be a powerful model system for the study of learning and memory. This animal displays several simple forms of nonassociative learning, such as habituation, dishabituation, and sensitization (Pinsker et al. 1970(Pinsker et al. , 1973Carew et al. 1971), but also more complex forms of associative learning such as classical, operant, and fear conditioning (Carew et al. , 1983Walters et al. 1981; Lechner et al. 2000a,b;Brembs et al. 2002). The strength of this model system arises from the relative simplicity of its central nervous system (CNS), which contains a small number of neurons, some of which are well characterized both morphologically and electrophysiologically. Thus, one can study a specific synaptic connection in different animals subjected to a wide variety of behavioral training protocols. For this reason, it has been possible to discover many of the mechanisms of learning and memory in this animal at the behavioral, cellular, and molecular levels, and provide direct evidence that certain forms of learning rely on the plasticity of individual synaptic connections (for review, see Kandel 2001).One of the best characterized forms of learning in Aplysia is sensitization, in which a noxious stimulus facilitates an animal's pre-existing response to the presentation of another innocuous stimulus. It has been most thoroughly studied in the defensive reflex responses of Aplysia. For example, a mild tactile stimulus applied to the tail evokes the retraction of respiratory organs (gill and siphon) inside the mantle cavity situated on the back of the animal. The stre...

show abstract

Signal recognition and integration by GS-stimulated adenylyl cyclases

Cited by 57 publications

References 29 publications

Distinct Characteristics of the Basal Activities of Adenylyl Cyclases 2 and 6

Distinct Characteristics of the Basal Activities of Adenylyl Cyclases 2 and 6

A Key Role for Protein Kinase A in Homologous Desensitization of the β2-Adrenergic Receptor Pathway in S49 Lymphoma Cells

Multiple Serotonergic Mechanisms Contributing to Sensitization in Aplysia: Evidence of Diverse Serotonin Receptor Subtypes

Contact Info

Product

Resources

About