scholarly journals Anchoring of Protein Kinase A-Regulatory Subunit IIα to Subapically Positioned Centrosomes Mediates Apical Bile Canalicular Lumen Development in Response to Oncostatin M but Not cAMP

2007 ◽  
Vol 18 (7) ◽  
pp. 2745-2754 ◽  
Author(s):  
Kacper A. Wojtal ◽  
Dick Hoekstra ◽  
Sven C.D. van IJzendoorn
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Membrane Trafficking ◽  
Oncostatin M ◽  
Regulatory Subunit ◽  
Apical Surface ◽  
Dependent Manner ◽  
Anchoring Protein ◽  
Pka Regulatory Subunit ◽  
Kinase A

Oncostatin M and cAMP signaling stimulate apical surface-directed membrane trafficking and apical lumen development in hepatocytes, both in a protein kinase A (PKA)-dependent manner. Here, we show that oncostatin M, but not cAMP, promotes the A-kinase anchoring protein (AKAP)-dependent anchoring of the PKA regulatory subunit (R)IIα to subapical centrosomes and that this requires extracellular signal-regulated kinase 2 activation. Stable expression of the RII-displacing peptide AKAP-IS, but not a scrambled peptide, inhibits the association of RIIα with centrosomal AKAPs and results in the repositioning of the centrosome from a subapical to a perinuclear location. Concomitantly, common endosomes, but not apical recycling endosomes, are repositioned from a subapical to a perinuclear location, without significant effects on constitutive or oncostatin M-stimulated basolateral-to-apical transcytosis. Importantly, however, the expression of the AKAP-IS peptide completely blocks oncostatin M-, but not cAMP-stimulated apical lumen development. Together, the data suggest that centrosomal anchoring of RIIα and the interrelated subapical positioning of these centrosomes is required for oncostatin M-, but not cAMP-mediated, bile canalicular lumen development in a manner that is uncoupled from oncostatin M-stimulated apical lumen-directed membrane trafficking. The results also imply that multiple PKA-mediated signaling pathways control apical lumen development and that subapical centrosome positioning is important in some of these pathways.

scholarly journals Inhibition of serine/threonine phosphatase enhances arachidonic acid-induced [Ca2+]i via protein kinase A

2009 ◽  
Vol 296 (1) ◽  
pp. C88-C96 ◽  
Author(s):  
Tomoyuki Saino ◽  
Eileen L. Watson
Keyword(s):  
Arachidonic Acid ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Cell Types ◽  
Regulatory Subunit ◽  
Calyculin A ◽  
Anchoring Protein ◽  
Pka Regulatory Subunit ◽  
Pp2a Inhibitor ◽  
Kinase A

Arachidonic acid (AA) regulates intracellular calcium concentration ([Ca2+]i) in a variety of cell types including salivary cells. In the present study, the effects of serine/threonine phosphatases on AA-induced Ca2+ signaling in mouse parotid acini were determined. Mice were euthanized with CO2. Treatment of acini with the serine/threonine phosphatase inhibitor calyculin A blocked both thapsigargin- and carbachol-induced Ca2+ entry but resulted in an enhancement of AA-induced Ca2+ release and entry. Effects were mimicked by the protein phosphatase-1 (PP1) inhibitor tautomycin but were inhibited by the PP2A inhibitor okadaic acid. The protein kinase A (PKA) inhibitor PKI(14-22) significantly attenuated AA-induced enhancement of Ca2+ release and entry in the presence of calyculin A, whereas it had no effect on calyculin A-induced inhibition of thapsigargin-induced Ca2+ responses. The ryanodine receptor (RyR) inhibitor, tetracaine, and StHt-31, a peptide known to competitively inhibit type II PKA regulatory subunit binding to PKA-anchoring protein (AKAP), abolished calyculin A enhancement of AA-induced Ca2+ release and entry. StHt-31 also abolished forskolin potentiation of 4-chloro-3-ethylphenol (4-CEP) and AA on Ca2+ release but had no effect on 8-(4-methoxyphenylthio)-2′- O-methyladenosine-3′,5′-cAMP potentiation of 4-CEP responses. Results suggest that inhibition of PP1 results in an enhancement of AA-induced [Ca2+]i via PKA, AKAP, and RyRs.

scholarly journals Complex effects of kinase localization revealed by compartment-specific regulation of protein kinase A activity

2021 ◽  
Author(s):  
Rebecca LaCroix ◽  
Benjamin Lin ◽  
Andre Levchenko
Keyword(s):  
Cell Migration ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Kinase Activity ◽  
Single Cells ◽  
Regulatory Subunit ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Specific Regulation ◽  
Kinase A

SummaryKinase activity in signaling networks frequently depends on regulatory subunits that can both inhibit activity by interacting with the catalytic subunits and target the kinase to distinct molecular partners and subcellular compartments. Here, using a new synthetic molecular interaction system, we show that translocation of a regulatory subunit of the protein kinase A (PKA-R) to the plasma membrane has a paradoxical effect on the membrane kinase activity. It can both enhance it at lower translocation levels, even in the absence of signaling inputs, and inhibit it at higher translocation levels, suggesting its role as a linker that can both couple and decouple signaling processes in a concentration-dependent manner. We further demonstrate that superposition of gradients of PKA-R abundance across single cells can control the directionality of cell migration, reversing it at high enough input levels. Thus complex in vivo patterns of PKA-R localization can drive complex phenotypes, including cell migration.

Stress-induced cytoplasmic localisation of the protein kinase A (PKA) regulatory subunit Bcy1 requires Sch9 and Yak1

2001 ◽  
Vol 1 (S1) ◽  
Author(s):  
G Griffioen ◽  
P Branduardi ◽  
B Ballarini ◽  
J Norbeck ◽  
B Baroni ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Regulatory Subunit ◽  
Pka Regulatory Subunit ◽  
Kinase A

scholarly journals PRKAR1A gene analysis and protein kinase A activity in endometrial tumors

2012 ◽  
Vol 19 (4) ◽  
pp. 457-462 ◽  
Author(s):  
A Tsigginou ◽  
E Bimpaki ◽  
M Nesterova ◽  
A Horvath ◽  
S Boikos ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Regulatory Subunit ◽  
Normal Endometrium ◽  
Protein Levels ◽  
Normal Tissues ◽  
Subunit Expression ◽  
Dependent Protein ◽  
Pka Regulatory Subunit ◽  
Kinase A

PRKAR1A codes for the type 1a regulatory subunit (RIα) of the cAMP-dependent protein kinase A (PKA), an enzyme with an important role in cell cycle regulation and proliferation. PKA dysregulation has been found in various tumors, and PRKAR1A-inactivating mutations have been reported in mostly endocrine neoplasias. In this study, we investigated PKA activity and the PRKAR1A gene in normal and tumor endometrium. Specimens were collected from 31 patients with endometrial cancer. We used as controls 41 samples of endometrium that were collected from surrounding normal tissues or from women undergoing gynecological operations for other reasons. In all samples, we sequenced the PRKAR1A-coding sequence and studied PKA subunit expression; we also determined PKA activity and cAMP binding. PRKAR1A mutations were not found. However, PKA regulatory subunit protein levels, both RIα and those of regulatory subunit type 2b (RIIβ), were lower in tumor samples; cAMP binding was also lower in tumors compared with normal endometrium (P<0.01). Free PKA activity was higher in tumor samples compared with that of control tissue (P<0.01). There are significant PKA enzymatic abnormalities in tumors of the endometrium compared with surrounding normal tissue; as these were not due to PRKAR1A mutations, other mechanisms affecting PKA function ought to be explored.

scholarly journals AKAP350 Interaction with cdc42 Interacting Protein 4 at the Golgi Apparatus

2004 ◽  
Vol 15 (6) ◽  
pp. 2771-2781 ◽  
Author(s):  
M. Cecilia Larocca ◽  
Ryan A. Shanks ◽  
Lan Tian ◽  
David L. Nelson ◽  
Donn M. Stewart ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Golgi Apparatus ◽  
Protein Kinase A ◽  
Membrane Trafficking ◽  
Interacting Protein ◽  
Anchoring Protein ◽  
Regulatory Effects ◽  
Related Proteins ◽  
Kinase A

The A kinase anchoring protein 350 (AKAP350) is a multiply spliced type II protein kinase A anchoring protein that localizes to the centrosomes in most cells and to the Golgi apparatus in epithelial cells. In the present study, we sought to identify AKAP350 interacting proteins that could yield insights into AKAP350 function at the Golgi apparatus. Using yeast two-hybrid and pull-down assays, we found that AKAP350 interacts with a family of structurally related proteins, including FBP17, FBP17b, and cdc42 interacting protein 4 (CIP4). CIP4 interacts with the GTP-bound form of cdc42, with the Wiscott Aldrich Syndrome group of proteins, and with microtubules, and exerts regulatory effects on cytoskeleton and membrane trafficking. CIP4 is phosphorylated by protein kinase A in vitro, and elevation of intracellular cyclic AMP with forskolin stimulates in situ phosphorylation of CIP4. Our results indicate that CIP4 interacts with AKAP350 at the Golgi apparatus and that either disruption of this interaction by expressing the CIP4 binding domain in AKAP350, or reduction of AKAP350 expression by RNA interference leads to changes in Golgi structure. The results suggest that AKAP350 and CIP4 influence the maintenance of normal Golgi apparatus structure.

scholarly journals PCTK1 Regulates Integrin-Dependent Spindle Orientation via Protein Kinase A Regulatory Subunit KAP0 and Myosin X

2015 ◽  
Vol 35 (7) ◽  
pp. 1197-1208 ◽  
Author(s):  
Sayaka Iwano ◽  
Ayaka Satou ◽  
Shigeru Matsumura ◽  
Naoyuki Sugiyama ◽  
Yasushi Ishihama ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Functional Module ◽  
Regulatory Subunit ◽  
Spindle Orientation ◽  
Β1 Integrin ◽  
Dependent Manner ◽  
Dependent Cell ◽  
Myosin X ◽  
Kinase A

Integrin-dependent cell-extracellular matrix (ECM) adhesion is a determinant of spindle orientation. However, the signaling pathways that couple integrins to spindle orientation remain elusive. Here, we show that PCTAIRE-1 kinase (PCTK1), a member of the cyclin-dependent kinases (CDKs) whose function is poorly characterized, plays an essential role in this process. PCTK1 regulates spindle orientation in a kinase-dependent manner. Phosphoproteomic analysis together with an RNA interference screen revealed that PCTK1 regulates spindle orientation through phosphorylation of Ser83 on KAP0, a regulatory subunit of protein kinase A (PKA). This phosphorylation is dispensable for KAP0 dimerization and for PKA binding but is necessary for its interaction with myosin X, a regulator of spindle orientation. KAP0 binds to the FERM domain of myosin X and enhances the association of myosin X-FERM with β1 integrin. This interaction between myosin X-FERM and β1 integrin appeared to be crucial for spindle orientation control. We propose that PCTK1-KAP0-myosin X-β1 integrin is a functional module providing a link between ECM and the actin cytoskeleton in the ECM-dependent control of spindle orientation.

scholarly journals A-kinase anchoring protein 8L interacts with mTORC1 and promotes cell growth

2020 ◽  
Vol 295 (23) ◽  
pp. 8096-8105 ◽  
Author(s):  
Chase H. Melick ◽  
Delong Meng ◽  
Jenna L. Jewell
Keyword(s):  
Protein Kinase ◽  
Cell Growth ◽  
Protein Kinase A ◽  
Terminal Region ◽  
Regulatory Subunit ◽  
Interacting Protein ◽  
Regulatory Subunits ◽  
Anchoring Protein ◽  
Regulate Cell Growth ◽  
Kinase A

mTOR complex 1 (mTORC1) senses nutrients to mediate anabolic processes within the cell. Exactly how mTORC1 promotes cell growth remains unclear. Here, we identified a novel mTORC1-interacting protein called protein kinase A anchoring protein 8L (AKAP8L). Using biochemical assays, we found that the N-terminal region of AKAP8L binds to mTORC1 in the cytoplasm. Importantly, loss of AKAP8L decreased mTORC1-mediated processes such as translation, cell growth, and cell proliferation. AKAPs anchor protein kinase A (PKA) through PKA regulatory subunits, and we show that AKAP8L can anchor PKA through regulatory subunit Iα. Reintroducing full-length AKAP8L into cells restored mTORC1-regulated processes, whereas reintroduction of AKAP8L missing the N-terminal region that confers the interaction with mTORC1 did not. Our results suggest a multifaceted role for AKAPs in the cell. We conclude that mTORC1 appears to regulate cell growth, perhaps in part through AKAP8L.

scholarly journals A Small Novel A-Kinase Anchoring Protein (AKAP) That Localizes Specifically Protein Kinase A-Regulatory Subunit I (PKA-RI) to the Plasma Membrane

2012 ◽  
Vol 287 (52) ◽  
pp. 43789-43797 ◽  
Author(s):  
Pepijn P. Burgers ◽  
Yuliang Ma ◽  
Luigi Margarucci ◽  
Mason Mackey ◽  
Marcel A. G. van der Heyden ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Regulatory Subunit ◽  
Anchoring Protein ◽  
Kinase A

scholarly journals Phosphorylation of protein kinase A (PKA) regulatory subunit RIα by protein kinase G (PKG) primes PKA for catalytic activity in cells

2018 ◽  
Vol 293 (12) ◽  
pp. 4411-4421 ◽  
Author(s):  
Kristofer J. Haushalter ◽  
Darren E. Casteel ◽  
Andrea Raffeiner ◽  
Eduard Stefan ◽  
Hemal H. Patel ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Protein Kinase G ◽  
Regulatory Subunit ◽  
Pka Regulatory Subunit ◽  
Kinase A ◽  
In Cells
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