Disruptions to protein kinase A localization in adrenal pathology DOI
Mitchell H. Omar

Biochemical Society Transactions, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 4, 2024

Cell signaling fidelity requires specificity in protein-protein interactions and precise subcellular localization of molecules. In the case protein phosphorylation, many kinases phosphatases exhibit promiscuous substrate pairing therefore require targeting to modify appropriate substrates avoid cross-talk among different pathways. past 10 years, researchers have discovered investigated how loss specific for kinase A catalytic subunit (PKAc) lead cortisol-producing adenomas debilitating stress disorder adrenal Cushing's syndrome. This article reviews classical studies regarding PKA glucocorticoid-producing cells synthesizes recent evidence disrupted selective regulatory pathology.

Language: Английский

Protein kinase A and local signaling in cancer DOI
Kacey J. Rosenthal, John D. Gordan, John D. Scott

et al.

Biochemical Journal, Journal Year: 2024, Volume and Issue: 481(22), P. 1659 - 1677

Published: Nov. 14, 2024

Protein kinase A (PKA) is a basophilic implicated in the modulation of many cell-signaling and physiological processes. PKA also contributes to cancer-relevant events such as growth factor action, cell cycle control, migration tumor metabolism. Germline somatic mutations PKA, gene amplifications, chromosome rearrangements that encode fusions, are linked growing number malignant neoplasms. Mislocalization by exclusion from A-Kinase Anchoring (AKAP) signaling islands further underlies cancer progression. This article highlights influence AKAP local action selected hallmarks cancer. We feature utility inhibitor drugs frontline future anti-cancer therapies.

Language: Английский

Citations

6
The evolution of AKAPs and emergence of PKA isotype selective anchoring determinants DOI Creative Commons
Jerome Falcone,

Kristan H. Cleveland,

Mingu Kang

et al.

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108480 - 108480

Published: April 1, 2025

Cyclic AMP is a versatile signaling molecule utilized throughout the eukaryotic domain. A frequent use to activate protein kinase (PKA), serine/threonine that drives many physiological responses. Spatiotemporal organization of PKA occurs though association with A-kinase anchoring proteins (AKAPs). Sequence alignments and phylogenetic analyses trace evolution regulatory (R) catalytic (C) subunits, AKAPs from emergence metazoans. preferentially associate type I (RI), or II (RII) subunits diverged at advent vertebrate clade. Type including smAKAP contain an FA motif positions 1 2 their amphipathic binding helices. Fluorescence recovery after photobleaching (FRAP) measurements indicate associates RI (T 1/2. 4.37 ± 1.2 sec; n=3) as compared RII 2.19 0.5 n=3). Parallel studies measured AKAP79 half times 8.74 0.3 sec (n=3) for 14.42 2.1 respectively. Introduction AF motifs either ends helix biases full length toward reduce corticosterone release adrenal cells by 61.5 0.8 % (n=3). Conversely, substitution YA beginning pair leucine's abrogates anchoring. Thus, have evolved base metazoan clade into specialized proteins.

Language: Английский

Citations

0
The ascent of AKAPs, from architectural elements to kinase anchors: a perspective DOI Creative Commons
Jerome Falcone, John D. Scott

Biochemical Journal, Journal Year: 2025, Volume and Issue: 482(10), P. 485 - 498

Published: May 1, 2025

Protein interaction domains binding to their recognition motifs are the nuts and bolts that hold macromolecular complexes together. Point mutations gene fusions drive evolutionary changes in these interactors have created a burgeoning repertoire of protein scaffolds. A-Kinase anchoring proteins (AKAPs) archetypal signal organizing compartmentalize kinase A (PKA) inside cell. An amino-terminal docking dimerization (d/d) domain on regulatory subunit binds with high affinity an amphipathic helix AKAP. This perspective introduces new group called interacting preceded advent AKAP-PKA interface. We also examine various paths used by gain PKA function.

Language: Английский

Citations

0
Long AKAP18 isoforms anchor ubiquitin specific proteinases and coordinate calcium reuptake at the sarcoplasmic reticulum DOI Creative Commons

Taeyeop Park,

Katherine A. Forbush, Yong Li

et al.

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 110317 - 110317

Published: May 1, 2025

Language: Английский

Citations

0
Anchored PKA synchronizes adrenergic phosphoregulation of cardiac Cav1.2 channels. DOI Creative Commons

Lipeng Wang,

Yi Chen,

Jin Li

et al.

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 300(9), P. 107656 - 107656

Published: Aug. 10, 2024

Language: Английский

Citations

2
Spatiotemporal control of kinases and the biomolecular tools to trace activity DOI Creative Commons
Jeremy C. Burton,

Fredejah Royer,

Neil Grimsey

et al.

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: unknown, P. 107846 - 107846

Published: Oct. 1, 2024

Language: Английский

Citations

0
Disruptions to protein kinase A localization in adrenal pathology DOI
Mitchell H. Omar

Biochemical Society Transactions, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 4, 2024

Cell signaling fidelity requires specificity in protein-protein interactions and precise subcellular localization of molecules. In the case protein phosphorylation, many kinases phosphatases exhibit promiscuous substrate pairing therefore require targeting to modify appropriate substrates avoid cross-talk among different pathways. past 10 years, researchers have discovered investigated how loss specific for kinase A catalytic subunit (PKAc) lead cortisol-producing adenomas debilitating stress disorder adrenal Cushing's syndrome. This article reviews classical studies regarding PKA glucocorticoid-producing cells synthesizes recent evidence disrupted selective regulatory pathology.

Language: Английский

Citations

0