16 Structure, function, and regulation of human cAMP-dependent protein kinases

Taskén, Kjetil; Bs, Skålhegg; Tasken, Kristin Austlid; Solberg, Rigmor; Knutsen, Helle Katrine; Fo, Levy; Sandberg, Mårten; Ørstavik, Sigurd; Larsen, Terje S.; Ak, Johansen; Vang, Torkel; Hp, Schrader; Nt, Reinton; Km, Torgersen; Hansson,; Jahnsen, Tore

doi:10.1016/s1040-7952(97)80019-5

Cited by 150 publications

(117 citation statements)

References 61 publications

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“…(3) Sanger sequencing analysis of coding exons 2 to 11 in our patients unraveled four previously undescribed heterozygous missense variants (c.524A>G, c.625A>G, c.806A>G, and c.879C>G) affecting exons 6, 7, and 9 ( Table 1, Fig. 1).…”

Section: Prkar1a Genetic Defects In Our Seriesmentioning

confidence: 60%

Screening of PRKAR1A and PDE4D in a Large Italian Series of Patients Clinically Diagnosed With Albright Hereditary Osteodystrophy and/or Pseudohypoparathyroidism

Elli

Bordogna

Sanctis

et al. 2016

Journal of Bone and Mineral Research

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The cyclic adenosine monophosphate (cAMP) intracellular signaling pathway mediates the physiological effects of several hormones and neurotransmitters, acting by the activation of G-protein coupled receptors (GPCRs) and several downstream intracellular effectors, including the heterotrimeric stimulatory G-protein (Gs), the cAMP-dependent protein kinase A (PKA), and cAMP-specific phosphodiesterases (PDEs). Defective G-protein-mediated signaling has been associated with an increasing number of disorders, including Albright hereditary osteodistrophy (AHO) and pseudohypoparathyroidism (PHP), a heterogeneous group of rare genetic metabolic disorders resulting from molecular defects at the GNAS locus. Moreover, mutations in PRKAR1A and PDE4D genes have been recently detected in patients with acrodysostosis (ACRDYS), showing a skeletal and endocrinological phenotype partially overlapping with AHO/PHP. Despite the high detection rate of molecular defects by currently available molecular approaches, about 30% of AHO/PHP patients still lack a molecular diagnosis, hence the need to screen patients negative for GNAS epi/genetic defects also for chromosomal regions and genes associated with diseases that undergo differential diagnosis with PHP. According to the growing knowledge on Gsa-cAMP signaling-linked disorders, we investigated our series of patients (n ¼ 81) with a clinical diagnosis of PHP/AHO but negative for GNAS anomalies for the presence of novel genetic variants at PRKAR1A and PDE4D genes. Our work allowed the detection of 8 novel missense variants affecting genes so far associated with ACRDYS in 9 patients. Our data further confirm the molecular and clinical overlap among these disorders. We present the data collected from a large series of patients and a brief review of the literature in order to compare our findings with already published data; to look for PRKAR1A/PDE4D mutation spectrum, recurrent mutations, and mutation hot spots; and to identify specific clinical features associated with ACRDYS surveillance during follow-up.

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Section: Prkar1a Genetic Defects In Our Seriesmentioning

confidence: 60%

Screening of PRKAR1A and PDE4D in a Large Italian Series of Patients Clinically Diagnosed With Albright Hereditary Osteodystrophy and/or Pseudohypoparathyroidism

Elli

Bordogna

Sanctis

et al. 2016

Journal of Bone and Mineral Research

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“…A large number of cytosolic and nuclear proteins have been identified as substrates for PKA (Tasken et al 1997). PKA phosphorylates numerous metabolic enzymes, including glycogen synthase and phosphorylase kinase, which inhibits glycogen synthesis and promotes glycogen breakdown, respectively, and acetyl CoA carboxylase, which inhibits lipid synthesis.…”

Section: P Sassone-corsimentioning

confidence: 99%

The Cyclic AMP Pathway

Sassone–Corsi

2012

Cold Spring Harbor Perspectives in Biology

358

275

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“…In contrast, the upstream promoter region of the Aplysia RI gene (GenBank accession number AY387675) has no CRE but contains GC-rich elements (SP1 and AP2). Aplysia RI therefore appears to be a housekeeping gene like R subunit genes in other animals whose transcription normally is not regulated (Tasken et al, 1997).…”

Section: Increase In Aprii Is Critical For Long-term Facilitationmentioning

confidence: 99%

The Two Regulatory Subunits ofAplysiacAMP-Dependent Protein Kinase Mediate Distinct Functions in Producing Synaptic Plasticity

Liu¹,

Hu²,

Schacher³

et al. 2004

J. Neurosci.

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Activation of the cAMP-dependent protein kinase (PKA) is critical for both short-and long-term facilitation in Aplysia sensory neurons. There are two types of the kinase, I and II, differing in their regulatory (R) subunits. We cloned Aplysia RII; RI was cloned previously. Type I PKA is mostly soluble in the cell body whereas type II is enriched at nerve endings where it is bound to two prominent A kinaseanchoring-proteins (AKAPs). Disruption of the binding of RII to AKAPs by Ht31, an inhibitory peptide derived from a human thyroid AKAP, prevents both the short-and the long-term facilitation produced by serotonin (5-HT). During long-term facilitation, RII is transcriptionally upregulated; in contrast, the amount of RI subunits decreases, and previous studies have indicated that the decrease is through ubiquitin-proteosome-mediated proteolysis. Experiments with antisense oligonucleotides injected into the sensory neuron cell body show that the increase in RII protein is essential for the production of long-term facilitation. Using synaptosomes, we found that 5-HT treatment causes RII protein to increase at nerve endings. In addition, using reverse transcription-PCR, we found that RII mRNA is transported from the cell body to nerve terminals. Our results suggest that type I operates in the nucleus to maintain cAMP response element-binding protein-dependent gene expression, and type II PKA acts at sensory neuron synapses phosphorylating proteins to enhance release of neurotransmitter. Thus, the two types of the kinase have distinct but complementary functions in the production of facilitation at synapses of an identified neuron.

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16 Structure, function, and regulation of human cAMP-dependent protein kinases

Cited by 150 publications

References 61 publications

Screening of PRKAR1A and PDE4D in a Large Italian Series of Patients Clinically Diagnosed With Albright Hereditary Osteodystrophy and/or Pseudohypoparathyroidism

Screening of PRKAR1A and PDE4D in a Large Italian Series of Patients Clinically Diagnosed With Albright Hereditary Osteodystrophy and/or Pseudohypoparathyroidism

The Cyclic AMP Pathway

The Two Regulatory Subunits ofAplysiacAMP-Dependent Protein Kinase Mediate Distinct Functions in Producing Synaptic Plasticity

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