The type 1 alpha regulatory subunit (R1alpha) of cAMP-dependent protein kinase A (PKA) (PRKAR1A) is an important regulator of the serine-threonine kinase activity catalyzed by the PKA holoenzyme. Carney complex (CNC) describes the association 'of spotty skin pigmentation, myxomas, and endocrine overactivity'; CNC is in essence the latest form of multiple endocrine neoplasia to be described and ...

The Carney complex (CNC) is a dominantly inherited syndrome responsible mainly for spotty skin pigmentation (lentiginosis), endocrine overactivity, and cardiac myxomas. Adrenocorticotropic hormone independent Cushing's syndrome due to primary pigmented nodular adrenocortical disease (PPNAD) is a main characteristic of CNC. PPNAD is a very rare cause of Cushing's syndrome due to a primary bilate...

OBJECTIVE Primary pigmented nodular adrenocortical disease (PPNAD) is the main endocrine manifestation of Carney complex, a multiple neoplasia syndrome caused by PRKAR1A gene mutations. The presence of PRKAR1A loss of heterozygosity (LOH) in adrenocortical tumorigenesis remains controversial. The aim of the present study is to investigate the presence of PRKAR1A LOH in adrenocortical cells in a...

OBJECTIVE Carney complex (CNC) is a rare autosomal dominant multiple neoplasia syndrome characterized by the presence of endocrine and non-endocrine tumors. More than 125 different germline mutations of the protein Kinase A type 1-α regulatory subunit (PRKAR1A) gene have been reported. We present a novel PRKAR1A gene germline mutation in a patient with severe osteoporosis and recurrent vertebra...

Background Cardiac myxomas are benign tumors that commonly arise within the left atria. Familial cardiac myxomas are a part of Carney Complex (CNC), an autosomal dominant multiple neoplasia syndrome caused by germline mutations in PRKAR1A. Seven percent of cardiac myxomas are associated with CNC. To date, the genetic basis of isolated cardiac myxomas (ICM), however, has not been fully elucidate...

BACKGROUND Protein kinase A signaling has long been known to play an important role in cardiac function. Dysregulation of the protein kinase A system, caused by mutation of the protein kinase A regulatory subunit gene PRKAR1A, causes the inherited tumor syndrome Carney complex, which includes cardiac myxomas as one of its cardinal features. Mouse models of this genetic defect have been unsatisf...

Carney complex (CNC) is a rare disease associated with multiple neoplasias, including a predisposition to pancreatic tumors; it is caused most frequently by the inactivation of the PRKAR1A gene, a regulator of the cyclic AMP (cAMP)-dependent kinase (PKA). The method used was to create null alleles of prkar1a in mouse cells expressing pdx1 (Δ-Prkar1a). We found that these mice developed endocrin...

Cardiac myxoma is the most common cardiac tumour. Most lesions occur sporadically, but occasional lesions develop in patients with Carney complex, a syndrome characterized by cardiac myxoma, spotty pigmentation, and endocrine overactivity. Two-thirds of patients with Carney complex harbour germline mutations in PRKAR1A, which encodes the type I regulatory subunit of protein kinase A (PKA). Most...

Carney complex (CNC) is caused by PRKAR1A-inactivating mutations. PRKAR1A encodes the regulatory subunit type I-alpha (RIalpha) of the cAMP-dependent kinase (PKA) holoenzyme; how RIalpha insufficiency leads to tumorigenesis remains unclear. In many cells PKA inhibits the extracellular receptor kinase (ERK1/2) cascade of the mitogen-activated protein kinase (MAPK) pathway leading to inhibition o...

Proper regulation of the cAMP-dependent protein kinase (protein kinase A, PKA) is necessary for cellular homeostasis, and dysregulation of this kinase is crucial in human disease. Mouse embryonic fibroblasts (MEFs) lacking the PKA regulatory subunit Prkar1a show altered cell morphology and enhanced migration. At the molecular level, these cells showed increased phosphorylation of cofilin, a cru...