Phosphorylation of the Type‐II Regulatory Subunit of Cyclic‐AMP‐Dependent Protein Kinase by Glycogen Synthase Kinase 3 and Glycogen Synthase Kinase 5

Hemmings, Brian A.; Aitken, Alastair; Cohen, Philip; Rymond, Michael; Hofmann, Franz

doi:10.1111/j.1432-1033.1982.tb06896.x

Cited by 171 publications

(11 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This mechanism would include an increase in NR2A stabilization in postsynaptic membranes, the delivery to synapses or even modulation of NR2A expression (Groc et al, 2009; Perez-Otano and Ehlers, 2005). MAGUK proteins such as PSD-95 (Soto et al, 2004), kinases such as PKC (Allende and Allende, 1995) or PKA (Carmichael et al, 1982; Hemmings et al, 1982), phosphatases such as PP2A (Heriche et al, 1997), PP2C (Pinna and Meggio, 1997) or PTP1B (Jung et al, 1998) and a large number of transcription factors (Blanquet, 2000; Meggio and Pinna, 2003) are some of the candidate proteins phosphorylated by CK2 that might affect NR2A synaptic expression. An alternative and appealing explanation for our observations is that the NMDAR 2A/2B subunit switch is a mechanism with two sequential and coupled stages, in which the synaptic removal of NR2B is required to allow NR2A synaptic incorporation.…”

Section: Discussionmentioning

confidence: 99%

Casein Kinase 2 Regulates the NR2 Subunit Composition of Synaptic NMDA Receptors

Sanz-Clemente

Matta

Isaac

et al. 2010

Neuron

180

202

View full text Add to dashboard Cite

SUMMARY NMDA receptors (NMDARs) play a central role in development, synaptic plasticity and neurological disease. NMDAR subunit composition defines their biophysical properties and downstream signaling. Casein kinase 2 (CK2) phosphorylates the NR2B subunit within its PDZ-binding domain; however, the consequences for NMDAR localization and function are unclear. Here we show that CK2 phosphorylation of NR2B regulates synaptic NR2B and NR2A in response to activity. We find that CK2 phosphorylates NR2B, but not NR2A, to drive NR2B-endocytosis and remove NR2B from synapses resulting in an increase in synaptic NR2A expression. During development there is an activity-dependent switch from NR2B to NR2A at cortical synapses. We observe an increase in CK2 expression and NR2B phosphorylation over this same critical period, and show that the acute activity-dependent switch in NR2 subunit composition at developing hippocampal synapses requires CK2 activity. Thus CK2 plays a central role in determining the NR2 subunit content of synaptic NMDARs.

show abstract

Section: Discussionmentioning

confidence: 99%

Casein Kinase 2 Regulates the NR2 Subunit Composition of Synaptic NMDA Receptors

Sanz-Clemente

Matta

Isaac

et al. 2010

Neuron

180

202

View full text Add to dashboard Cite

show abstract

“…Interestingly, phosphorylation of PKA RII by glycogen synthase kinase has been described earlier. 67 On PKA RIIR we observed one specific phosphorylation site at Ser97. This site was earlier identified as an autophosphorylation site that reduces the affinity of the regulatory subunit 2,71,72 AKAPs identified in this experiment are depicted in red when abundantly present in our PKA-enriched fraction (among top 25 proteins based on Fabb), in green proteins in the top 50, but not top 25, and in yellow the lower abundant AKAPs of our pull down.…”

mentioning

confidence: 84%

Diversity of cAMP-Dependent Protein Kinase Isoforms and Their Anchoring Proteins in Mouse Ventricular Tissue

et al. 2007

View full text Add to dashboard Cite

Using a chemical proteomics approach, we efficiently enriched for the generally low abundant cAMP signaling proteins, and their interactors, directly from mouse ventricular tissue. The presence of undesired contaminating (noncyclic) nucleotide-binding proteins was diminished using a tailored sequential elution protocol. Through further optimization of this affinity purification and elution protocol, we were able to detect all known protein kinase A regulatory isoforms (PKA-R). Furthermore, 11 different A-kinase anchoring proteins (AKAPs) were detected. A proposed fusion protein of paralemmin 2 and AKAP2 could be decisively established as a novel AKAP at the protein level in ventricular tissue. When comparing this dataset of cAMP-affinity purified proteins with earlier data obtained with immobilized cGMP from rat ventricular tissue, we observe a large overlap in the retained proteins but also some clear differences. Furthermore, implementation of an in-depth analysis of in vivo phosphorylation sites on PKA-R revealed the presence of several differentially phosphorylated PKA-R isoforms. This illustrates yet another layer of functional regulation in cyclic nucleotide signaling. In general, our improved chemical proteomics screen offers a broad, but detailed, view on nature's complex diversity in cyclic nucleotide signaling mechanisms. Possibly different AKAP-isoforms may direct differentially phosphorylated PKA-R isoforms to different cellular compartments, providing a multifaceted platform for just this kinase.

show abstract

“…We deem the first possibility likely because cluster II serines comprise several Gsk3 consensus sites (7). Moreover, mammalian RII subunits can be phosphorylated in vitro by purified Gsk3 (33), suggesting that such phosphorylations on cAPKs are evolutionarily conserved.…”

Section: Discussionmentioning

confidence: 99%

Feedback Inhibition on Cell Wall Integrity Signaling by Zds1 Involves Gsk3 Phosphorylation of a cAMP-dependent Protein Kinase Regulatory Subunit

Griffioen¹,

Swinnen

Thevelein

2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

We report here that budding yeast cAMP-dependent protein kinase (cAPK) is controlled by heat stress. A rise in temperature from 30 to 37°C was found to result in both a higher expression and an increased cytoplasmic localization of its regulatory subunit Bcy1. Both of these effects required phosphorylation of serines located in its localization domain. Surprisingly, classic cAPK-controlled processes were found to be independent of Bcy1 phosphorylation, indicating that these modifications do not affect cAPK activity as such. Alternatively, phosphorylation may recruit cAPK to, and thereby control, a specific subset of (perhaps novel) cAPK targets that are presumably localized extranuclearly. Zds1 and Zds2 may play a role in this process, since these were found required to retain hyperphosphorylated Bcy1 in the cytoplasm at 37°C. Mck1, a homologue of mammalian glycogen synthase kinase 3 and a downstream component of the heat-activated Pkc1-Slt2/Mpk1 cell wall integrity pathway, is partly responsible for hyperphosphorylations of Bcy1. Remarkably, Zds1 appears to act as a negative regulator of cell wall integrity signaling, and this activity is dependent in part on the phosphorylation status of Bcy1. Thus, Mck1 phosphorylation of Bcy1 and Zds1 may constitute an unprecedented negative feedback control on the cell wall integrity-signaling pathway.In eukaryotes from yeast to humans, cAMP-dependent protein kinases (cAPKs) 1 are ubiquitous signaling proteins. A structural characteristic of cAPKs is that the regulatory and catalytic activities are not covalently linked but are represented by two different subunits. The inactive cAPK holoenzyme consists of a regulatory (R) subunit homodimer with two catalytic subunits associated to it. Binding of the second messenger cAMP to the R-dimer leads to dissociation of the holoenzyme, and the released catalytic subunits are then able to phosphorylate protein substrates at serine or threonine residues comprising a defined consensus sequence.cAPK recognition sequences, however, are of low complexity and therefore insufficient to poise proteins as specific cAPK substrates. Moreover, in a single cell, cAPK can participate in several parallel pathways that control the phosphorylation status of specific substrates in response to different triggers. Compartmentalization of signaling molecules provides an important level of control to achieve additional signaling specificity. In multicellular organisms, protein kinase A anchor proteins (AKAPs) have been identified that target cAPK holoenzymes to specific subcellular locations (for a recent review, see Ref. 1 and references therein). These AKAPs function as adapters; one domain associates with an AKAP-binding surface created by dimerization of the R-subunit, whereas another distinct domain interacts with a cellular structure or organelle. AKAPmediated targeting of cAPK is thought to confer spatio-temporal control of cAPK signaling in order to phosphorylate substrates specifically.In the unicellular eukaryote, Saccharomyces cerevisiae cAPK i...

show abstract

Phosphorylation of the Type‐II Regulatory Subunit of Cyclic‐AMP‐Dependent Protein Kinase by Glycogen Synthase Kinase 3 and Glycogen Synthase Kinase 5

Cited by 171 publications

References 48 publications

Casein Kinase 2 Regulates the NR2 Subunit Composition of Synaptic NMDA Receptors

Casein Kinase 2 Regulates the NR2 Subunit Composition of Synaptic NMDA Receptors

Diversity of cAMP-Dependent Protein Kinase Isoforms and Their Anchoring Proteins in Mouse Ventricular Tissue

Feedback Inhibition on Cell Wall Integrity Signaling by Zds1 Involves Gsk3 Phosphorylation of a cAMP-dependent Protein Kinase Regulatory Subunit

Contact Info

Product

Resources

About