Signaling diversity of PKA achieved via a Ca2+-cAMP-PKA oscillatory circuit. 2011

Qiang Ni, and Ambhighainath Ganesan, and Nwe-Nwe Aye-Han, and Xinxin Gao, and Michael D Allen, and Andre Levchenko, and Jin Zhang
Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Many protein kinases are key nodal signaling molecules that regulate a wide range of cellular functions. These functions may require complex spatiotemporal regulation of kinase activities. Here, we show that protein kinase A (PKA), Ca(2+) and cyclic AMP (cAMP) oscillate in sync in insulin-secreting MIN6 beta cells, forming a highly integrated oscillatory circuit. We found that PKA activity was essential for this oscillatory circuit and was capable of not only initiating the signaling oscillations but also modulating their frequency, thereby diversifying the spatiotemporal control of downstream signaling. Our findings suggest that exquisite temporal control of kinase activity, mediated via signaling circuits resulting from cross-regulation of signaling pathways, can encode diverse inputs into temporal parameters such as oscillation frequency, which in turn contribute to proper regulation of complex cellular functions in a context-dependent manner.

UI MeSH Term Description Entries
D008853 Microscopy The use of instrumentation and techniques for visualizing material and details that cannot be seen by the unaided eye. It is usually done by enlarging images, transmitted by light or electron beams, with optical or magnetic lenses that magnify the entire image field. With scanning microscopy, images are generated by collecting output from the specimen in a point-by-point fashion, on a magnified scale, as it is scanned by a narrow beam of light or electrons, a laser, a conductive probe, or a topographical probe. Compound Microscopy,Hand-Held Microscopy,Light Microscopy,Optical Microscopy,Simple Microscopy,Hand Held Microscopy,Microscopy, Compound,Microscopy, Hand-Held,Microscopy, Light,Microscopy, Optical,Microscopy, Simple
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002413 Cations, Divalent Positively charged atoms, radicals or groups of atoms with a valence of plus 2, which travel to the cathode or negative pole during electrolysis. Divalent Cations
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000242 Cyclic AMP An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH. Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor
D015153 Blotting, Western Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes. Immunoblotting, Western,Western Blotting,Western Immunoblotting,Blot, Western,Immunoblot, Western,Western Blot,Western Immunoblot,Blots, Western,Blottings, Western,Immunoblots, Western,Immunoblottings, Western,Western Blots,Western Blottings,Western Immunoblots,Western Immunoblottings
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D050417 Insulin-Secreting Cells A type of pancreatic cell representing about 50-80% of the islet cells. Beta cells secrete INSULIN. Pancreatic beta Cells,beta Cells, Pancreatic,Pancreatic B Cells,B Cell, Pancreatic,B Cells, Pancreatic,Cell, Insulin-Secreting,Cells, Insulin-Secreting,Insulin Secreting Cells,Insulin-Secreting Cell,Pancreatic B Cell,Pancreatic beta Cell,beta Cell, Pancreatic

Related Publications

Qiang Ni, and Ambhighainath Ganesan, and Nwe-Nwe Aye-Han, and Xinxin Gao, and Michael D Allen, and Andre Levchenko, and Jin Zhang
November 2020, eLife,
Qiang Ni, and Ambhighainath Ganesan, and Nwe-Nwe Aye-Han, and Xinxin Gao, and Michael D Allen, and Andre Levchenko, and Jin Zhang
November 1997, The American journal of physiology,
Qiang Ni, and Ambhighainath Ganesan, and Nwe-Nwe Aye-Han, and Xinxin Gao, and Michael D Allen, and Andre Levchenko, and Jin Zhang
May 2004, Science (New York, N.Y.),
Qiang Ni, and Ambhighainath Ganesan, and Nwe-Nwe Aye-Han, and Xinxin Gao, and Michael D Allen, and Andre Levchenko, and Jin Zhang
March 2021, Membranes,
Qiang Ni, and Ambhighainath Ganesan, and Nwe-Nwe Aye-Han, and Xinxin Gao, and Michael D Allen, and Andre Levchenko, and Jin Zhang
October 2014, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology,
Qiang Ni, and Ambhighainath Ganesan, and Nwe-Nwe Aye-Han, and Xinxin Gao, and Michael D Allen, and Andre Levchenko, and Jin Zhang
November 2016, Journal of neuroinflammation,
Qiang Ni, and Ambhighainath Ganesan, and Nwe-Nwe Aye-Han, and Xinxin Gao, and Michael D Allen, and Andre Levchenko, and Jin Zhang
January 2023, Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society,
Qiang Ni, and Ambhighainath Ganesan, and Nwe-Nwe Aye-Han, and Xinxin Gao, and Michael D Allen, and Andre Levchenko, and Jin Zhang
November 2011, Journal of molecular and cellular cardiology,
Qiang Ni, and Ambhighainath Ganesan, and Nwe-Nwe Aye-Han, and Xinxin Gao, and Michael D Allen, and Andre Levchenko, and Jin Zhang
February 2020, Cell biology international,
Qiang Ni, and Ambhighainath Ganesan, and Nwe-Nwe Aye-Han, and Xinxin Gao, and Michael D Allen, and Andre Levchenko, and Jin Zhang
January 2016, Biologie aujourd'hui,
Copied contents to your clipboard!