Mys Protein Regulates Protein Kinase A Activity by Interacting with Regulatory Type Iα Subunit during Vertebrate Development

Kotani, Tomoya; Iemura, Shun‐ichiro; Natsume, Tohru; Kawakami, Koichi; Yamashita, Masakane

doi:10.1074/jbc.m109.070995

Cited by 5 publications

(4 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, we can infer that in Drosophila, the tight regulation of PKA activity, and thus its positive and negative roles, dictates the pathway's outcome. Interestingly, high basal PKA activity in the absence of Hh is not the main mechanism by which cells inhibit Hh pathway activity, as levels of PKA activity are minimal in many cells (Amieux et al, 2002, Kotani et al, 2010. Indeed, keeping global PKA activity levels at the lower threshold is important in cells because PKA is involved in a myriad of cellular processes.…”

Section: Pka Dual Role In Drosophila Hh Signaling Pathwaymentioning

confidence: 99%

“…This prevents the activity of the catalytic subunit by masking its core kinase domain (Taylor et al, 2008, Kim et al, 2005. Remarkably, a large proportion of PKA in zebrafish and mouse embryos is usually present in an inactive state and only a limited activation of PKA occurs (Amieux et al, 2002, Kotani et al, 2010. Binding of cAMP to the regulatory subunit of PKA promotes its dissociation from the catalytic subunit, allowing the free catalytic subunit to phosphorylate its substrates (Taylor et al, 2008).…”

Section: Pka Structurementioning

confidence: 99%

See 1 more Smart Citation

Extensive crosstalk of G protein-coupled receptors with the Hedgehog signalling pathway

Saad

Hipfner

2021

Development

View full text Add to dashboard Cite

Hedgehog (Hh) ligands orchestrate tissue patterning and growth by acting as morphogens, dictating different cellular responses depending on ligand concentration. Cellular sensitivity to Hh ligands is influenced by heterotrimeric G protein activity, which controls production of the second messenger 3',5'-cyclic adenosine monophosphate (cAMP). cAMP in turn activates Protein kinase A (PKA), which functions as an inhibitor and (uniquely in Drosophila) an activator of Hh signalling. A few mammalian Gαi- and Gαs-coupled G protein-coupled receptors (GPCRs) have been shown to influence Sonic Hh (Shh) responses in this way. To determine if this is a more general phenomenon, we carried out an RNAi screen targeting GPCRs in Drosophila. RNAi-mediated depletion of more than 40% of GPCRs tested either decreased or increased Hh responsiveness in the developing Drosophila wing, closely matching the effects of Gαs and Gαi depletion, respectively. Genetic analysis indicated that the orphan GPCR Mthl5 lowers cAMP levels to attenuate Hh responsiveness. Our results identify Mthl5 as a new Hh signalling pathway modulator in Drosophila and suggest that many GPCRs may crosstalk with the Hh pathway in mammals.

show abstract

Section: Pka Dual Role In Drosophila Hh Signaling Pathwaymentioning

confidence: 99%

Section: Pka Structurementioning

confidence: 99%

Extensive crosstalk of G protein-coupled receptors with the Hedgehog signalling pathway

Saad

Hipfner

2021

Development

View full text Add to dashboard Cite

show abstract

“…Taken together, the results obtained with differentially identified kinases, phosphatases, and regulatory proteins in Trpv1 KO and WT mice indicate that changes observed in the Trpv1 KO mice orchestrate an increased breakdown of glycogen. In this context, PKA activity is positively regulated by PRRC1 [84] and ARFGEF2 (also known as BIG2), which acts as an A kinase-anchoring protein (AKAP) [85]. Then, PKA activates protein phosphatase 2A (PP2A complex) [86].…”

Section: Differential Interactions Of Kinases and Phosphatases Underl...mentioning

confidence: 99%

Lack of TRPV1 Channel Modulates Mouse Gene Expression and Liver Proteome with Glucose Metabolism Changes

Lacerda

Gomes

Zanetti

et al. 2022

IJMS

View full text Add to dashboard Cite

To investigate the role of the transient receptor potential channel vanilloid type 1 (TRPV1) in hepatic glucose metabolism, we analyzed genes related to the clock system and glucose/lipid metabolism and performed glycogen measurements at ZT8 and ZT20 in the liver of C57Bl/6J (WT) and Trpv1 KO mice. To identify molecular clues associated with metabolic changes, we performed proteomics analysis at ZT8. Liver from Trpv1 KO mice exhibited reduced Per1 expression and increased Pparα, Pparγ, Glut2, G6pc1 (G6pase), Pck1 (Pepck), Akt, and Gsk3b expression at ZT8. Liver from Trpv1 KO mice also showed reduced glycogen storage at ZT8 but not at ZT20 and significant proteomics changes consistent with enhanced glycogenolysis, as well as increased gluconeogenesis and inflammatory features. The network propagation approach evidenced that the TRPV1 channel is an intrinsic component of the glucagon signaling pathway, and its loss seems to be associated with increased gluconeogenesis through PKA signaling. In this sense, the differentially identified kinases and phosphatases in WT and Trpv1 KO liver proteomes show that the PP2A phosphatase complex and PKA may be major players in glycogenolysis in Trpv1 KO mice.

show abstract

“…These transgenic fish have been useful for various studies in developmental biology, genomics and neurobiology. For example, a novel hoxC transcript was revealed by the SAGp22A line [ 4 ], new functions for the tcf7 gene and the synembryn-like gene were uncovered using HG21C and HGn8H [ 9 ], mitochondrion-rich cells on the skin were visualized using HG9B [ 11 ], dilatation of the cardiac ventricle was analyzed using SAG4A [ 12 ], the misty somites gene encoding a maternal factor involved in somitogenesis was discovered in SAG20A [ 13 , 14 ], innervation of hair cells by afferent neurons was visualized in HGn39D [ 15 ], and nasal-temporal patterning of the retina by Fgf signaling was demonstrated using HGn42A [ 16 ]. More recent examples include studies of cell-fate determination in the notochord using SAGFF214A [ 17 ], characterization of the somatotopic projections of the lateral line afferent neurons in the CNS using hspGFF53A [ 18 ], sex-reversal in the fancl mutant HG10A [ 19 ], patterning of the lymphatic system (SAGFF27C;[ 20 ]), and lens fiber differentiation (SAGFF168A;[ 21 ]).…”

Section: Introductionmentioning

confidence: 99%

zTrap: zebrafish gene trap and enhancer trap database

et al. 2010

Self Cite

View full text Add to dashboard Cite

BackgroundWe have developed genetic methods in zebrafish by using the Tol2 transposable element; namely, transgenesis, gene trapping, enhancer trapping and the Gal4FF-UAS system. Gene trap constructs contain a splice acceptor and the GFP or Gal4FF (a modified version of the yeast Gal4 transcription activator) gene, and enhancer trap constructs contain the zebrafish hsp70l promoter and the GFP or Gal4FF gene. By performing genetic screens using these constructs, we have generated transgenic zebrafish that express GFP and Gal4FF in specific cells, tissues and organs. Gal4FF expression is visualized by creating double transgenic fish carrying a Gal4FF transgene and the GFP reporter gene placed downstream of the Gal4-recognition sequence (UAS). Further, the Gal4FF-expressing cells can be manipulated by mating with UAS effector fish. For instance, when fish expressing Gal4FF in specific neurons are crossed with the UAS:TeTxLC fish carrying the tetanus neurotoxin gene downstream of UAS, the neuronal activities are inhibited in the double transgenic fish. Thus, these transgenic fish are useful to study developmental biology and neurobiology.DescriptionTo increase the usefulness of the transgenic fish resource, we developed a web-based database named zTrap http://kawakami.lab.nig.ac.jp/ztrap/. The zTrap database contains images of GFP and Gal4FF expression patterns, and genomic DNA sequences surrounding the integration sites of the gene trap and enhancer trap constructs. The integration sites are mapped onto the Ensembl zebrafish genome by in-house Blat analysis and can be viewed on the zTrap and Ensembl genome browsers. Furthermore, zTrap is equipped with the functionality to search these data for expression patterns and genomic loci of interest. zTrap contains the information about transgenic fish including UAS reporter and effector fish.ConclusionzTrap is a useful resource to find gene trap and enhancer trap fish lines that express GFP and Gal4FF in desired patterns, and to find insertions of the gene trap and enhancer trap constructs that are located within or near genes of interest. These transgenic fish can be utilized to observe specific cell types during embryogenesis, to manipulate their functions, and to discover novel genes and cis-regulatory elements. Therefore, zTrap should facilitate studies on genomics, developmental biology and neurobiology utilizing the transgenic zebrafish resource.

show abstract

Mys Protein Regulates Protein Kinase A Activity by Interacting with Regulatory Type Iα Subunit during Vertebrate Development

Cited by 5 publications

References 53 publications

Extensive crosstalk of G protein-coupled receptors with the Hedgehog signalling pathway

Extensive crosstalk of G protein-coupled receptors with the Hedgehog signalling pathway

Lack of TRPV1 Channel Modulates Mouse Gene Expression and Liver Proteome with Glucose Metabolism Changes

zTrap: zebrafish gene trap and enhancer trap database

Contact Info

Product

Resources

About