Minireview: PRKAR1A: Normal and Abnormal Functions

Bossis, Ioannis; Stratakis, Constantine A.

doi:10.1210/en.2004-0900

Cited by 185 publications

(178 citation statements)

References 77 publications

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“…Although PKARI␣ may act as a "tumor suppressor" in CNC, previous studies have also reported that PKARI␣ facilitates the cell proliferative signaling of hormones and growth factors in certain types of cancer cells (46) and depletion of PKARI␣ effectively inhibits transcription of certain genes and growth of tumor cells (47). Thus, PKARI␣ may augment or inhibit cellular proliferation in a cell type-specific manner.…”

Section: Pp2a Exists In a Complex With Rsk1⅐pka⅐d-akap1 And Ht31mentioning

confidence: 99%

The PKARIα Subunit of Protein Kinase A Modulates the Activation of p90RSK1 and Its Function

Chaturvedi

Cohen

Taunton

et al. 2009

Journal of Biological Chemistry

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Cyclic AMP-dependent protein kinase (PKA) 3 plays a pivotal role in manifesting an array of biological actions ranging from cell proliferation and tumorigenesis to increased inotropic and chronotropic effects in the heart as well as regulation of long term potentiation and memory. The PKA holoenzyme is a heterotetramer and consists of two catalytic (PKAc) subunits bound to a dimer of regulatory subunits. To date, four isoforms of the PKAc (PKAc␣, PKAc␤, PKAc␥, and PKAc␦) and four isoforms of the regulatory subunits (RI␣, RI␤, RII␣, and RII␤) have been described (1). The various isoforms of PKA subunits are expressed differently in a tissue-and cell-specific manner (2). In addition to binding and inhibiting the activity of PKAc via their pseudo substrate region (3-6), the R subunits also interact with PKA-anchoring proteins (AKAPs) and facilitate the localization of PKA in specific subcellular compartments (7,8). More than 50 AKAP family members have been described, and although most of these have a higher affinity for the RII subunits (9), certain AKAPs such as D-AKAP1 and D-AKAP2 preferentially bind the PKARI␣ subunit (10 -12). Because the AKAPs also bind other signaling molecules such as phosphatases (PP2B) and kinases (protein kinase C), they act as scaffolds to organize and integrate specific signaling events within specific compartments in the cells (7,8,13,14).We have shown that the PKARI␣ and PKAc␣ subunits of PKA interact with the inactive and active forms of p90 RSK1 (RSK1), respectively (15). Binding of inactive RSK1 to PKARI␣ decreases the interactions between PKARI␣ and PKAc, whereas the association of active RSK1 with PKAc increases interactions between PKARI␣ and PKAc such that larger amounts of cAMP are required to activate PKAc in the presence of active RSK1 (15). Moreover, the indirect (via subunits of PKA) interaction of RSK1 with AKAPs is required for the nuclear localization of active RSK1 (15), and disruption of the interactions of RSK1⅐PKA complex from AKAPs results in increased cytoplasmic distribution of active RSK1 with a concomitant increase in phosphorylation of its cytosolic substrates such as BAD and reduced cellular apoptosis (15). These findings show the functional and biological significance of RSK1⅐ PKA⅐AKAP interactions.Besides inhibiting PKAc activity, the physiological role of PKARI␣ is underscored by the findings that mutations in the PKAR1A gene that result in haploinsufficiency of PKARI␣ are

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Section: Pp2a Exists In a Complex With Rsk1⅐pka⅐d-akap1 And Ht31mentioning

confidence: 99%

The PKARIα Subunit of Protein Kinase A Modulates the Activation of p90RSK1 and Its Function

Chaturvedi

Cohen

Taunton

et al. 2009

Journal of Biological Chemistry

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“…It can occur in isolated form, or as the main component of Carney syndrome [4]. Carney syndrome is an autosomal dominant disease caused by inactivating mutations of the PRKAR1A gene (chromosome 17q22-24) [6]. The PRKAR1A gene encodes the regulatory subunit of kinase-A [7].…”

Section: Discussionmentioning

confidence: 99%

Dwustronny pierwotny pigmentowany rozrost drobnoguzkowy nadnerczy jako składnik zespołu Carney — opis przypadku

Sikorska

Papierska

Mojs

et al. 2017

Endokrynologia Polska

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“…Em cerca de 60% dos pacientes com CC, uma mutação foi identi-ficada no gene da proteína kinase dependente de cAMP (PRKAR1A), principal mediador do sistema cAMP, diretamente envolvido na via de sinalização de ACTH. Mutações no gene PRKAR1A, localizado no 17q22-24, foram identificadas em adenomas adrenais, porém não em carcinomas adrenais; por outro lado, LOH dessa região foi encontrada em 23% dos adenomas e em 53% dos carcinomas adrenocorticais (37,38).…”

Section: Bases Moleculares Dos Tumores Adrenocorticaisunclassified

Tumores adrenocorticais na criança: da abordagem clínica à avaliação molecular

Antonini

Colli²,

Ferro

et al. 2011

Arq Bras Endocrinol Metab

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sumárioTumores do córtex adrenal (TCA) são mais frequentes em crianças, mas podem ocorrer em qualquer faixa etária. São classificados como funcionantes, não funcionantes (predominam no adulto), e mistos. O diagnóstico é baseado na avaliação clínica, hormonal e exames de imagem. Em crianças, o método de escolha para diferenciar entre benigno ou maligno é a classificação baseada no estadiamento do tumor. Alguns marcadores moleculares merecem destaque: além de mutações inativadoras no gene supressor tumoral TP53, há evidências de envolvimento do IGF2 em 90% de TAC malignos, e mutações no éxon 3 do gene CTNNB1 foram encontradas em 6% dos TAC pediátricos. Além disso, microRNAs podem atuar como reguladores negativos da expressão gênica e participar da tumorigênese adrenocortical. Métodos para análise da expressão gênica permitem identificar TCA com prognóstico bom ou ruim, e espera-se que esses estudos possam facilitar o desenvolvimento de drogas para tratar pacientes de acordo com as vias de sinalização específicas que estiverem alteradas. Arq Bras Endocrinol Metab. 2011;55(8):599-606 Descritores Tumor do córtex adrenal; doenças da adrenal; fatores de crescimento; proteína supressora de tumor P53; biologia molecular summArY Adrenocortical tumors (ACT) are more frequent during childhood, but they can appear at any age. ACTs can be classified in functioning, nonfunctioning (mainly observed in adults) and mixed. The diagnosis is based on clinical, biochemical findings and imaging. In children, in order to classify ACT as benign or malignant, tumor staging classification is recommended. Regarding molecular markers some studies should be taken into account: besides TP53 mutations, previous studies have also provided evidences of IGF2 involvement in 90% of the malignant ACT. Mutations altering exon 3 of CTNNB1 gene have been found in 6% of childhood ACTs. In addition, microRNAs can act as negative regulators of gene expression by targeting mRNA controlling cell growth, differentiation and apoptosis and have been implicated in adrenal tumorigenesis. High-throughput methods to analyze genome-wide expression have been developed over the last decade and identified a subset of tumors with good or poor prognosis. In the future, these studies can provide the basis of specific drug development, which can treat patients according to specific altered signaling pathway. Arq Bras Endocrinol Metab. 2011;55(8):599-606 Keywords Adrenal cortex tumor; adrenal gland diseases; molecular biology growth factors; tumor suppressor protein P53 iNTroDuÇÃo O s tumores adrenocorticais (TAC) apresentam incidência bimodal, sendo mais comuns nos primeiros cinco anos de vida e entre a 4ª e 5ª décadas de vida. Em todas as faixas etárias esses tumores são mais frequentes no sexo feminino (1,2). Sua incidência varia de acordo com a região geográfica, sendo dez a quinze vezes mais elevada no Sul e Sudeste do Brasil, onde ocorrem apro-

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Minireview: PRKAR1A: Normal and Abnormal Functions

Cited by 185 publications

References 77 publications

The PKARIα Subunit of Protein Kinase A Modulates the Activation of p90RSK1 and Its Function

The PKARIα Subunit of Protein Kinase A Modulates the Activation of p90RSK1 and Its Function

Dwustronny pierwotny pigmentowany rozrost drobnoguzkowy nadnerczy jako składnik zespołu Carney — opis przypadku

Tumores adrenocorticais na criança: da abordagem clínica à avaliação molecular

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