Interaction of AIP with protein kinase A (cAMP-dependent protein kinase)

Schernthaner-Reiter, Marie Helene; Trivellin, Giampaolo; Stratakis, Constantine A.

doi:10.1093/hmg/ddy166

Cited by 27 publications

(26 citation statements)

References 40 publications

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“…Silencing of AIP resulted in PKA pathway activation, and furthermore, the activation was disproportionately elevated under PDE4specific inhibition, suggesting an additional functional interaction. Of note, the mutant AIP p.R304* interacted to a lesser degree with both PKA subunits (76). Disrupted mutant AIP-PDE4A5 interaction has also been previously reported (77).…”

Section: Aip Mutations In Fipa and Sporadic Pituitary Adenomassupporting

confidence: 64%

“…A strongly positive correlation between AIP and Gαi-2 protein expression has also been confirmed in sporadic somatotropinomas (73). The complex interplay between AIP and PKA signaling is further supported by the evidence that AIP interacts physically with both the regulatory (R1α) and the catalytic (Cα) subunits of PKA separately, as well as in complex (76). AIP overexpression led to a decrease in nuclear Cα expression and total PKA activity.…”

Section: Aip Mutations In Fipa and Sporadic Pituitary Adenomasmentioning

confidence: 66%

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Somatic and germline mutations in the pathogenesis of pituitary adenomas

Vandeva

Daly

Pétrossians

et al. 2019

European Journal of Endocrinology

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Pituitary adenomas are frequently occurring neoplasms that produce clinically significant disease in 1:1000 of the general population. The pathogenesis of pituitary tumors is a matter of interest as it could help to improve diagnosis and treatment. Until recently, however, disruptions in relatively few genes were known to predispose to pituitary tumor formation. In the last decade, several more genes and pathways have been described. Germline pathogenic variants in the aryl hydrocarbon receptor-interacting protein (AIP) gene were found in familial or sporadic pituitary adenomas, usually with an aggressive clinical course. Cyclin-dependent kinase inhibitor 1B (CDKN1B) pathogenic variants lead to multiple endocrine neoplasia type 4 (MEN4) syndrome, in which pituitary adenomas can occur. Xq26.3 duplications involving the gene GPR101 cause X-linked acrogigantism. The pheochomocytoma and/or paraganglioma with pituitary adenoma association (3PAs) syndrome suggests that pathogenic variants in the genes of the succinate dehydrogenase complex or MYC-associated factor X (MAX) might be involved in pituitary tumorigenesis. New recurrent somatic alterations were also discovered in pituitary adenomas, such as, ubiquitin-specific protease 8 (USP8) and USP48 pathogenic variants in corticotropinomas. The aim of the present review is to provide an overview of the genetic pathophysiology of pituitary adenomas and their clinical relevance.

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Section: Aip Mutations In Fipa and Sporadic Pituitary Adenomassupporting

confidence: 64%

Section: Aip Mutations In Fipa and Sporadic Pituitary Adenomasmentioning

confidence: 66%

Somatic and germline mutations in the pathogenesis of pituitary adenomas

Vandeva

Daly

Pétrossians

et al. 2019

European Journal of Endocrinology

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“…For instance, AIP has been found to interact with both the catalytic (PRKACA) and the regulatory (PRKAR1A) subunits of PKA (Schernthaner-Reiter et al 2018). An interaction between AIP and PRKACA was demonstrated in the presence of HSP90, and cytoplasmic co-localisation of AIP and PRAKACA was observed (Hernandez-Ramirez et al 2018, Schernthaner-Reiter et al 2018, suggesting that the AIP/HSP90 complex could regulate PKA localisation and potentially affect the interaction between the catalytic and regulatory subunits of PKA. Moreover, AIP has been shown to interact with members of the type 4 phosphodiesterases family, such as PDE4A5 (Bolger et al 2003) -enzymes involved in the degradation of cAMP.…”

Section: Aryl Hydrocarbon Receptor-interacting Proteinmentioning

confidence: 99%

Germline and mosaic mutations causing pituitary tumours: genetic and molecular aspects

Pepe

Korbonits

Iacovazzo

2019

Journal of Endocrinology

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While 95% of pituitary adenomas arise sporadically without a known inheritable predisposing mutation, in about 5% of the cases they can arise in a familial setting, either isolated (familial isolated pituitary adenoma or FIPA) or as part of a syndrome. FIPA is caused, in 15–30% of all kindreds, by inactivating mutations in the AIP gene, encoding a co-chaperone with a vast array of interacting partners and causing most commonly growth hormone excess. While the mechanisms linking AIP with pituitary tumorigenesis have not been fully understood, they are likely to involve several pathways, including the cAMP-dependent protein kinase A pathway via defective G inhibitory protein signalling or altered interaction with phosphodiesterases. The cAMP pathway is also affected by other conditions predisposing to pituitary tumours, including X-linked acrogigantism caused by duplications of the GPR101 gene, encoding an orphan G stimulatory protein-coupled receptor. Activating mosaic mutations in the GNAS gene, coding for the Gα stimulatory protein, cause McCune–Albright syndrome, while inactivating mutations in the regulatory type 1α subunit of protein kinase A represent the most frequent genetic cause of Carney complex, a syndromic condition with multi-organ manifestations also involving the pituitary gland. In this review, we discuss the genetic and molecular aspects of isolated and syndromic familial pituitary adenomas due to germline or mosaic mutations, including those secondary to AIP and GPR101 mutations, multiple endocrine neoplasia type 1 and 4, Carney complex, McCune–Albright syndrome, DICER1 syndrome and mutations in the SDHx genes underlying the association of familial paragangliomas and phaeochromocytomas with pituitary adenomas.

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“…Moreover, binding to PDE2A interrupts the nuclear translocation of the AhR complex possibly by local reduction in cAMP levels [57]. Quite recently, it has been demonstrated that AIP physically interacts with both the catalytic (PRKACA) and the regulatory (PRKAR1A) subunits of PKA [69]. Other interacting partners of AIP include the tyrosine kinase receptor, encoded by the RET protooncogene, a number of nuclear receptors including the peroxisome proliferator-activated receptor α ( PPARα), the glucocorticoid receptor, thyroid hormone receptor β1, cytoskeleton proteins such as TUBB and TUBB2A [57,70].…”

Section: Familial Isolated Pituitary Adenomasmentioning

confidence: 99%

Clinical and Molecular Update on Genetic Causes of Pituitary Adenomas

et al. 2020

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Pituitary adenomas are benign tumors with variable functional characteristics that can have a significant impact on patients. The majority arise sporadically, but an inherited genetic susceptibility is increasingly being recognized. Recent advances in genetics have widened the scope of our understanding of pituitary tumorigenesis. The clinical and genetic characteristics of pituitary adenomas that develop in the setting of germline-mosaic and somatic GNAS mutations (McCune–Albright syndrome and sporadic acromegaly), germline MEN1 mutations (multiple endocrine neoplasia type 1), and germline PRKAR1A mutations (Carney complex) have been well described. Non-syndromic familial cases of isolated pituitary tumors can occur as familial isolated pituitary adenomas (FIPA); mutations/deletions of the AIP gene have been found in a minority of these. Genetic alterations in GPR101 have been identified recently as causing X-linked acro-gigantism (X-LAG) leading to very early-onset pediatric gigantism. Associations of pituitary adenomas with other tumors have been described in syndromes like multiple endocrine neoplasia type 4, pheochromocytoma-paraganglioma with pituitary adenoma association (3PAs) syndrome and some of their genetic causes have been elucidated. The genetic etiologies of a significant proportions of sporadic corticotropinomas have recently been identified with the discovery of USP8 and USP48 mutations. The elucidation of genetic and molecular pathophysiology in pituitary adenomas is a key factor for better patient management and effective follow-up.

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Interaction of AIP with protein kinase A (cAMP-dependent protein kinase)

Cited by 27 publications

References 40 publications

Somatic and germline mutations in the pathogenesis of pituitary adenomas

Somatic and germline mutations in the pathogenesis of pituitary adenomas

Germline and mosaic mutations causing pituitary tumours: genetic and molecular aspects

Clinical and Molecular Update on Genetic Causes of Pituitary Adenomas

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