Pkar1a

Cardiac myxoma is a relatively rare tumour, usually solitary, that occurs primarily in the left atrium of adults, but comprises only 30% of cardiac tumours in children. We recently treated a 12-year-old girl with multiple recurrent myxomas in three cardiac chambers(following surgical resection 3 years earlier). Genomic analysis showed the PKAR1A mutation typical for Carney complex.

BACKGROUND: The repertoire of protein expression along the renal tubule depends both on regulation of transcription and regulation of alternative splicing that can generate multiple proteins from a single gene. METHODS: A full-length, small-sample RNA-seq protocol profiled transcriptomes for all 14 renal tubule segments microdissected from mouse kidneys. RESULTS: This study identified >34,000 transcripts, including 3709 that were expressed in a segment-specific manner...

Mitochondria are essential sites for steroid hormone biosynthesis. Mitochondria in the steroidogenic cells of the adrenal, gonad, placenta and brain contain the cholesterol side-chain cleavage enzyme, P450scc, and its two electron-transfer partners, ferredoxin reductase and ferredoxin. This enzyme system converts cholesterol to pregnenolone and determines net steroidogenic capacity, so that it serves as the chronic regulator of steroidogenesis. Several other steroidogenic enzymes, including 3β-hydroxysteroid dehydrogenase, 11β-hydroxylase and aldosterone synthase also reside in mitochondria...

Adrenal gonadal, placental and brain mitochondria contain several steroidogenic enzymes, notably the cholesterol side chain cleavage enzyme, P450scc, which is the enzymatic rate-limiting step in steroidogenesis which determines cellular steroidogenic capacity. Even before this step, the access of cholesterol to this enzyme system is both rate-limiting and the site of acute regulation via the steroidogenic acute regulatory protein (StAR) which interacts with a complex multi-component 'transduceosome' on the outer mitochondrial membrane (OMM)...

We report the results of phosphoproteomic analysis of mouse thymoma cells treated with tributyltin oxide (TBTO), an immunotoxic compound. After cell lysis, phosphoproteins were isolated using Phosphoprotein Purification Kit, separated by SDS-PAGE and subsequently digested with trypsin. Phosphopeptides were enriched employing titanium dioxide, and the obtained fractions were analyzed by nano-LC-MS/MS. A total of 160 phosphoproteins and 328 phosphorylation sites were identified in thymoma cells. Among the differentially phosphorylated proteins identified in TBTO-treated cells were key enzymes, which catalyze rate-limiting steps in pathways that are sensitive to cellular energy status...

Oncogenes and tumor suppressor genes involved in most common cancers are not involved in the great majority of pituitary adenomas. Similarly, there is little evidence to suggest that the mutations involved in genetic syndromes associated with pituitary tumors (such as the gsp, MEN1, PKAR1A or AIP mutations) are common in sporadic tumors. A novel pituitary tumor transforming gene (PTTG, securin) has been identified which is over-expressed in most tumors--but it is unclear as to its causal role in oncogenesis...

Differentiated thyroid cancers (papillary--PTC and follicular--FTC) are the most common endocrine malignancies. The recent progresses in the understanding of PTC and FTC pathogenesis are summarized in this review. In PTC, a single mutation of BRAF (the gene for the B-type Raf kinase) (V600E) is responsible for the disease in 40-50% of patients, especially in older people and is associated with a poorer clinicopathological outcome. Due to these characteristics, its use as a specific diagnostic and prognostic marker for PTC in cytological specimens is being implemented...

The cAMP signaling pathway regulates growth of many cell types, including somatotrophs, thyrocytes, melanocytes, ovarian follicular granulosa cells, adrenocortical cells, and keratinocytes. Mutations of partners from the cAMP signaling cascade are involved in tumor formation. Thyroid-stimulating hormone (TSH) receptor and Gsalpha activating mutations have been detected in thyroid autonomous adenomas, Gsalpha mutations in growth hormone-secreting pituitary adenomas, and PKAR1A mutations in Carney complex, a multiple neoplasia syndrome...

Heterozygous loss of function mutations in human PKAR1A gene (PRKAR1A) have been identified in patients with Carney complex (CNC), an autosomal dominant familial multiple neoplasia syndrome displaying different endocrine tumors, including adrenocortical tumors, GH-secreting pituitary tumors and thyroid adenomas. Although PRKAR1A is encoded by a single gene, it is transcribed from at least two different promoters, adjacent to different first non-coding exons (1a and 1b), giving rise to alternately spliced transcripts coding for identical proteins...