Regulation of AKAP-Membrane Interactions by Calcium

Tao, Jiangchuan; Shumay, Elena; McLaughlin, Stuart; Wang, Hsien‐yu; Malbon, Craig C.

doi:10.1074/jbc.m601813200

Cited by 42 publications

(70 citation statements)

References 35 publications

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“…Moreover, a number of myristoylome proteins are thought to be dispensable, because they belong to duplicated genes or gene families. In addition, several myristoylated proteins are known to be fully active even in the absence of MYR (Zhu et al, 1995;Tao et al, 2006), which does not seem to be essential for the functions of these proteins. Most of the genes encoding proteins of the N-myristoylome are induced by biotic or abiotic stresses (for example, see Ishitani et al, 2000), suggesting that these genes probably correspond to nonessential functions.…”

Section: Nmt1 Is Required For Snrk1 Regulationmentioning

confidence: 99%

N-Myristoylation Regulates the SnRK1 Pathway inArabidopsis

et al. 2007

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Cotranslational and posttranslational modifications are increasingly recognized as important in the regulation of numerous essential cellular functions. N-myristoylation is a lipid modification ensuring the proper function and intracellular trafficking of proteins involved in many signaling pathways. Arabidopsis thaliana, like human, has two tightly regulated N-myristoyltransferase (NMT) genes, NMT1 and NMT2. Characterization of knockout mutants showed that NMT1 was strictly required for plant viability, whereas NMT2 accelerated flowering. NMT1 impairment induced extremely severe defects in the shoot apical meristem during embryonic development, causing growth arrest after germination. A transgenic plant line with an inducible NMT1 gene demonstrated that NMT1 expression had further effects at later stages. NMT2 did not compensate for NMT1 in the nmt1-1 mutant, but NMT2 overexpression resulted in shoot and root meristem abnormalities. Various data from complementation experiments in the nmt1-1 background, using either yeast or human NMTs, demonstrated a functional link between the developmental arrest of nmt1-1 mutants and the myristoylation state of an extremely small set of protein targets. We show here that protein N-myristoylation is systematically associated with shoot meristem development and that SnRK1 (for SNF1-related kinase) is one of its essential primary targets.

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Section: Nmt1 Is Required For Snrk1 Regulationmentioning

confidence: 99%

N-Myristoylation Regulates the SnRK1 Pathway inArabidopsis

et al. 2007

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“…AKAPs are localized to numerous cellular sites, including the plasma membrane (AKAP79, Yotiao, AKAP18, and Gravin) (Klauck et al, 1996; Fraser et al, 1998;Lin et al, 1998;Grove and Bruchey, 2001) as well as Golgi, centrosome, nucleus, mitochondria, and cytosol (Feliciello et al, 2001). Those AKAPs that are located at the plasma membrane use a number of different strategies for docking, including myristoylation (AKAP18 and Gravin) (Lin et al, 1996;Fraser et al, 1998), polybasic regions (AKAP79 and Gravin) (Streb and Miano, 2005;Tao et al, 2006), or as-yet-unknown mechanisms (Yotiao). One of the important features of AKAP complexes is the intricate feedback loops that are assembled to control temporal aspects of cAMP signaling.…”

Section: Akaps Anchor Pka and Other Components Of Camp Signalingmentioning

confidence: 99%

Adenylyl Cyclase–A-kinase Anchoring Protein Complexes: The Next Dimension in cAMP Signaling

Dessauer¹

2009

Mol Pharmacol

228

195

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The formation of multiprotein complexes is a repeated theme in biology ranging from the regulation of the extracellular signalregulated kinase and cAMP signaling pathways to the formation of postsynaptic density complexes or tight junctions. A-kinase anchoring proteins (AKAPs) are well known for their ability to scaffold protein kinase A and components upstream and downstream of cAMP production, including G protein-coupled receptors, cAMP-dependent Rap-exchange factors, and phosphodiesterases. Specific adenylyl cyclase (AC) isoforms have also been identified as components of AKAP complexes, namely AKAP79, Yotiao, and mAKAP. In this review, we summarize recent evidence for AC-AKAP complexes and requirements for compartmentalization of cAMP signaling. The ability of AKAPs to assemble intricate feedback loops to control spatiotemporal aspects of cAMP signaling adds yet another dimension to the classic cAMP pathway.The generation of cAMP and subsequent activation of protein kinase A (PKA) is one of the best understood signal transduction pathways. However, it remains unclear how the soluble second-messenger cAMP achieves any type of subcellular or molecular specificity. PKA phosphorylates a broad range of substrates but somehow manages to mediate precise phosphorylation events at specific sites within the cell. For example, stimulation of ␤1 adrenergic receptors (ARs), ␤2AR, or prostaglandin E1 receptors have clearly distinguishable effects on cardiac myocytes, despite each being coupled to adenylyl cyclase (AC) (Buxton and Brunton, 1983;Steinberg and Brunton, 2001). The follicle-stimulating hormone and luteinizing hormone also seem to use the same intracellular intermediates but activate different sets of genes in granulose cells (Conti, 2002). Measurements of cAMP using cyclic nucleotide-gated channels (CNGs or HCN) or fluorescence resonance energy transfer reporters based on PKA or EPAC have provided direct evidence for limited cAMP diffusion throughout the cell (Fischmeister et al., 2006;Berrera et al., 2008). Where cAMP is produced is also critical, because cAMP generated at the plasma membrane versus cytosol can have opposite effects on endothelial barrier function (Sayner et al., 2006). However, until recently, it was not clear how a restricted pool of cAMP generated by AC was specifically targeted to a select subset of effectors to give rise to distinct physiological outcomes. This problem is solved by tethering AC to complexes containing cAMP effectors and downstream targets. This review focuses on recent evidence that signalosomes formed by A-kinase anchoring proteins (AKAPs) help to coordinate cAMP synthesis and downstream signaling by assembling AC-AKAP complexes. cAMP Synthesis: Mammalian Adenylyl Cyclase IsoformsIn higher eukaryotes, two basic families of adenylyl cyclase exist: the G protein-regulated transmembrane adenylyl cyclase isoforms, and a soluble adenylyl cyclase. The latter AC is regulated by bicarbonate and calcium and is insensitive to forskolin or activated G␣ s (Kamenetsky et al....

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“…All proteins encoded by each transcript share Ͼ95% amino acid sequence identity encoded by a single large exon but differ only at their extreme N-terminal residues. For example, only the ␣ isoform encodes a product that is myristoylated (2), and this modification facilitates ␣ SSeCKS association with plasma membranes and vesicles of the endoplasmic reticulum (7,18,21), yet it is not sufficient for its plasma membrane targeting (22).…”

mentioning

confidence: 99%

v-Src-mediated Down-regulation of SSeCKS Metastasis Suppressor Gene Promoter by the Recruitment of HDAC1 into a USF1-Sp1-Sp3 Complex

Gelman

2007

Journal of Biological Chemistry

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SSeCKS (Src-suppressed C kinase substrate), also called gravin/AKAP12, is a large scaffolding protein with metastasis suppressor activity. Two major isoforms of SSeCKS are expressed in most cell and tissue types under the control of two independent promoters, designated ␣ and ␤, separated by 68 kb. SSeCKS transcript and protein levels are severely decreased in Src-and Ras-transformed fibroblasts and in many epithelial tumors. By dissecting its promoters with progressive deletion analysis, we identified the sequence between ؊106 and ؊49 in the ␣ proximal promoter as the minimal v-Src-responsive element, which contains E-and GC-boxes bound by USF1 and Sp1/ Sp3, respectively. Both E-and GC-boxes are crucial for v-Srcresponsive and basal promoter activities. v-Src does not alter USF1 binding levels at the E-box, but it increases Sp1/Sp3 binding to the GC-box despite no change in their cellular protein abundance. SSeCKS ␣ and ␤ transcript levels in v-Src/3T3 cells can be restored by treatment with the histone deacetylase inhibitor, trichostatin A, but not with the DNA demethylation agent, 5-azacytidine. Chromatin changes are found only on the ␣ promoter even though the ␤ proximal promoter contains a similar E-and GC-box arrangement. Recruitment of HDAC1 is necessary and sufficient to cause repression of ␣ proximal promoter activity, and the addition of Sp1 and/or Sp3 potentiates the repression. Our data suggest that suppression of the ␤ promoter is facilitated by Src-induced changes in the ␣ promoter chromatinization mediated by a USF1-Sp1-Sp3 complex.

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Regulation of AKAP-Membrane Interactions by Calcium

Cited by 42 publications

References 35 publications

N-Myristoylation Regulates the SnRK1 Pathway inArabidopsis

N-Myristoylation Regulates the SnRK1 Pathway inArabidopsis

Adenylyl Cyclase–A-kinase Anchoring Protein Complexes: The Next Dimension in cAMP Signaling

v-Src-mediated Down-regulation of SSeCKS Metastasis Suppressor Gene Promoter by the Recruitment of HDAC1 into a USF1-Sp1-Sp3 Complex

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