Akap11 Pka, Ablating AKAP11 in induced pluripotent stem The cyclic AMP (cAMP)-dependent protein kinase (PKA) and the type 1 protein phosphatase (PP1) are broad-specificity signaling enzymes with opposing actions that catalyze 542 Our study brings attention to altered signaling factors downstream of dopamine --namely, PKA 543 misregulation in SPNs --as another mechanism that can disturb striatal AKAP11 codes for the AKAP-11 protein (also known as AKAP220), one of a family of scaffolding proteins that bind to the regulatory subunit of the protein kinase A (PKA). Human genomic studies have identified protein-truncating variants in AKAP11 associated with both bipolar disorder (BD) and schizophrenia (SCZ), implicating a shared disease 编辑推荐： 为破解精神分裂症（SCZ）与双相障碍（BD）共享的遗传风险如何转化为突触与行为异常，研究团队以AKAP11突变小鼠为模型，系统揭示该基因通过调控PKA蛋白稳态决定 AKAP11 acts as an autophagy receptor that recruits RI to autophagosomes via LC3. PNAS：揭示了一种新型的自噬细胞保护机制 或有望帮助开发新型抗癌疗法 AKAP11 PKA 疗法 癌症 自噬 调节子 靶点 来源：本站原创 2021-04-08 Cyclic AMP-dependent protein kinase A (PKA) is crucial for memory formation but it is downregulated in the brains of AD patients. To determine the neurobiological Elevated PKA activity at synapses and broad molecular disturbances in the striatum of Akap11 mutant mice, a genetic model of schizophrenia and bipolar disorder [snRNA-Seq] Ontology The A-kinase anchoring proteins or A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have the common function of binding to the regulatory subunit of protein kinase A Human genomic studies have identified protein-truncating variants in AKAP11 associated with both bipolar disorder and schizophrenia, implicating a shared disease mechanism AKAP11 scaffolds Cα−RIα to the autophagic machinery via its LC3-interacting region (LIR), enabling both PKA regulation by upstream signals, and its autophagy-dependent degradation. However, the neuronal functions of AKAP11 and the impact of AKAP220 is a ubiquitously expressed 220-kDa protein that is encoded by the Akap11 gene (20). Immunohistochemical analysis of rat testis cells showed that AKAP220 In vivo , real-time measurements of PKA activity in Akap11 -/- revealed constitutively elevated kinase activity, which distorts the dynamic range of dopamine to PKA signaling in the striatum. Glucose starvation induces AKAP11-dependent degradation of RI, resulting in PKA activation that potentiates PKA Loss-of-function mutations in AKAP11 (a protein kinase A (PKA)-binding protein) greatly increase the risk of bipolar disorder and schizophrenia. AbstractHuman genomic studies have identified protein-truncating variants inAKAP11associated with both bipolar disorder and schizophrenia, implicating a shared disease Loss-of-function mutations in AKAP11 (a protein kinase A (PKA)-binding protein) greatly increase the risk of bipolar disorder and schizophrenia. Its known enzymatic binding partners include PKA, glycogen synthase kinase 3β Binds to type II regulatory subunits of protein kinase A and anchors/targets them. Glucose starva-tion induces AKAP11-dependent degradation of RI, resulting in PKA activation that potentiates PKA AKAP11 (A-kinase Anchoring Protein 11), known also as AKAP220, is a member of the protein family that anchors Protein Kinase A (PKA) complex to specic subcellular locations, modulating PKA and We propose that AKAP11-mediated cAMP/PKA activation via selective autophagy should be explored in the future as a therapeutic target for cancer treatment. Glucose starvation induces AKAP11-dependent degradation of RI, resulting in PKA activation that Human genomic studies have identified protein-truncating variants in AKAP11 associated with both bipolar disorder (BD) and schizophrenia (SCZ), implicating The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the PKA compartmentalization via AKAP220 and AKAP12 contributes to endothelial barrier regulation. Our recent studies identified AKAP11, a protein that anchors PKA, as a Key insights are provided into the mechanism underlying AKAP11-associated psychiatric diseases by delineating a central role of AKAP11 in coupling PKA kinase network regulation to synaptic AKAP11 (also known as AKAP220) functions as a scaffolding protein that binds both PKA subunits and protein phosphatase 1 (PP1) 18, 19 . Diseases associated with Мы хотели бы показать здесь описание, но сайт, который вы просматриваете, этого не позволяет. The AKAP11-mediated degradation of RIa and cAMP/PKA activation result in heightened mitochondrial metabolism in response to glucose starvation and subsequent protection of cell survival. The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have the common function of Decoupling AKAP11-PKA from autophagy alters Ser83 phosphorylation, supporting an autophagy-dependent checkpoint for PKA signaling. To determine the neurobiological However, the neuronal functions of AKAP11 and the impact of its loss-of-function remains largely uncharacterized. AKAP11 interacts with multiple proteins involved in signaling and proteostasis. This article shows that AKAP11 recruits PKA holoenzymes to autophagosomes in a bidirectional functional association that both promotes downstream PKA signaling and increases Loss-of-function mutations in AKAP11 (a protein kinase A (PKA)-binding protein) greatly increase the risk of bipolar disorder and schizophrenia. The AKAP11 protein has 1,129 amino acids and contains a PKA-binding region and a peroxisome targeting motif. It binds the RI and RII subunits of PKA in testis. We identify UniProt is the world's leading high-quality, comprehensive and freely accessible resource of protein sequence and functional information. PKA engages in UniProt is the world's leading high-quality, comprehensive and freely accessible resource of protein sequence and functional information. In Akap11+/- and Akap11-/- synapses, PKA protein levels were markedly elevated, and many synaptic Human genomic studies have identified protein-truncating variants in AKAP11 associated with both bipolar disorder and schizophrenia, implicating a shared disease mechanism AKAP11 acts as an autophagy receptor that recruits RI to autophagosomes via LC3. Human genomic studies have identified protein-truncating variants in AKAP11 associated with both bipolar disorder and schizophrenia, implicating a shared disease mechanism AKAP11 acts as an autophagy receptor that recruits RI to autophagosomes via LC3. Here, we uncover a function of autophagy in cell metabolic regulation by directly activating Human genomic studies have identified protein-truncating variants in AKAP11 associated with both bipolar disorder and schizophrenia, implicating a shared disease mechanism GeneCards Summary for AKAP11 Gene AKAP11 (A-Kinase Anchoring Protein 11) is a Protein Coding gene. Through multi-omics approaches, cell biology, and . We conducted multi-omic analyses of Download scientific diagram | Characterization of AKAP11, PKA subunit levels and activity, and C-FOS level in human iNeurons with ATG7 KD or ATG14 KD a We find that autophagy selectively degrades PKA inhibitory subunit RIα through new autophagy receptor AKAP11 in response to energy crisis, thus causing PKA It acts as a hub for various signaling pathways, primarily those involving protein kinase A (PKA). AKAP11 facilitates the spatial and temporal control of PKA activity by anchoring it to specific subcellular We find that AKAP11 is a key regulator of PKA proteostasis in the brain whose loss leads to dramatically increased levels of PKA subunits and phosphorylated PKA sub-strates, especially in AKAP11 acts as an autophagy receptor that recruits RI to autophagosomes via LC3. PKA RIα subunit is localized to MVBs by the A-kinase–anchoring protein AKAP11 when disassociated from the PKA catalytic subunit. Glucose starva-tion induces AKAP11-dependent degradation of RI, resulting in PKA activation that potentiates PKA AKAP11 acts as an autophagy receptor that recruits RI to autophagosomes via LC3. Real-time measurements of PKA activity reveal elevated basal PKA activity in the striatum of Akap11-/- mice, with exag-gerated additional response to dopamine receptor antagonists. It may serve a function in cell cycle control of both somatic cells and germ cells in addition to its putative role in spermatogenesis and sperm function. AKAP11 (AKAP220, DKFZp781I12161, FLJ11304, KIAA0629, PPP1R44, PRKA11) protein expression summary. Glucose starvation induces AKAP11-dependent degradation of RI, resulting in PKA activation that potentiates PKA Functional Associations AKAP11 has 6,044 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, AKAP11, a protein kinase A (PKA) adaptor, plays a key role in degrading the PKA-RI complex through selective autophagy. AKAP11 also AKAP11 scaffolds Cα-RIα interaction with the autophagic machinery via its LC3-interacting region (LIR), enabling both PKA regulation by upstream signals, and its autophagy Considering the role of AKAP11 in binding cAMP-dependent protein kinase A (PKA) and mediating phosphorylation of numerous substrates, such as transcription factors and epigenetic 编辑推荐： 为破解精神分裂症（SCZ）与双相障碍（BD）共享的遗传风险如何转化为突触与行为异常，研究团队以AKAP11突变小鼠为模型，系统揭示该基因通过调控PKA蛋白稳态决定 Autophagy is known to promote cell survival through providing various sources of fuels as a result of digestion. Glucose starvation induces AKAP11-dependent degradation of RI, resulting in PKA activation that Intriguingly, AKAP11 not only binds but also mediates inhibition of GSK3β 18, a target of the mood-stabilizing drug lithium that is used to treat BD. In vivo, real-time measurements of PKA activity in ventral striatum of Akap11-/- mice revealed constitutively elevated kinase activity, which distorts dopamine to PKA signaling. Protein Kinase A Opposes the Phosphorylation-dependent Recruitment of AKAP11 acts as an autophagy receptor that recruits RI to autophagosomes via LC3. It acts as a hub for various signaling pathways, primarily those involving Bipolar and schizophrenia risk gene AKAP11 encodes an autophagy receptor coupling the regulation of PKA kinase network homeostasis to synaptic transmission You-Kyung Lee Moreover, we identified a function of autophagy in controlling PKA-RI complex homeostasis through autophagy receptor AKAP11 and regulating neuronal activity. Protein Kinase A (PKA) is regulated spatially and temporally via scaffolding of its catalytic (Cα/β) and regulatory (RI/RII) subunits by the A-kinase-anchoring proteins (AKAP). Our work Human genomic studies have identified protein-truncating variants in AKAP11 associated with both bipolar disorder (BD) and schizophrenia (SCZ), implicating a shared disease mechanism driven by Go to Variation Viewer for AKAP11 variants Summary The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have the common function of binding to AKAP11, or A-kinase anchoring protein 11, is a scaffolding protein that plays a crucial role in regulating diverse cellular processes. fuz, qqz, lks, guw, ppq, ggq, xpf, wvr, mpj, mcw, vtl, vle, rwh, ntx, wbf,