caa a22 4500 606243054 CHVBK 20210128101322.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s12551-015-0170-x doi (NATIONALLICENCE)springer-10.1007/s12551-015-0170-x Discovery of allostery in PKA signaling [Elektronische Daten] [Ping Zhang, Alexandr Kornev, Jian Wu, Susan Taylor] Cyclic AMP (cAMP)-dependent protein kinase (PKA) was the second protein kinase to be identified, and the PKA catalytic (C)-subunit serves as a prototype for the large protein kinase superfamily that contains over 500 gene products. The protein kinases regulate many biological functions in eukaryotic cells and are now also a major therapeutic target. The discovery of PKA nearly 50years ago was quickly followed by the identification of the regulatory subunits that bind cAMP and release the catalytic activity from the holoenzyme. Thus in PKA we see the convergence of two major signaling mechanisms—protein phosphorylation and second messenger signaling through cAMP. Crystallography provides a foundation for understanding function, and detailed knowledge of the structure of the isolated regulatory (R)- and catalytic (C)-subunits has been extremely informative. Yet it is the R2C2 holoenzyme that predominates in cells, and the allosteric features of PKA signaling can only be fully appreciated by seeing the full-length protein. The symmetry and the quaternary constraints that one R:C heterodimer exerts on the other in the holoenzyme simply are not present in the isolated subunits or even in the R:C heterodimer. International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag Berlin Heidelberg, 2015 Cyclic AMP nationallicence cAMP-dependent protein kinase nationallicence PKA catalytic subunit nationallicence PKA regulatory subunit nationallicence Allostery nationallicence Zhang Ping Department of Pharmacology, University of California at San Diego, 9500 Gilman Dr., 92093-0654, La Jolla, CA, USA aut Kornev Alexandr Department of Pharmacology, University of California at San Diego, 9500 Gilman Dr., 92093-0654, La Jolla, CA, USA aut Wu Jian Department of Pharmacology, University of California at San Diego, 9500 Gilman Dr., 92093-0654, La Jolla, CA, USA aut Taylor Susan Department of Pharmacology, University of California at San Diego, 9500 Gilman Dr., 92093-0654, La Jolla, CA, USA aut Biophysical Reviews Springer Berlin Heidelberg 7/2(2015-06-01), 227-238 1867-2450 7:2<227 2015 7 12551 https://doi.org/10.1007/s12551-015-0170-x text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 review-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s12551-015-0170-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zhang Ping Department of Pharmacology, University of California at San Diego, 9500 Gilman Dr., 92093-0654, La Jolla, CA, USA aut NATIONALLICENCE 700 1- Kornev Alexandr Department of Pharmacology, University of California at San Diego, 9500 Gilman Dr., 92093-0654, La Jolla, CA, USA aut NATIONALLICENCE 700 1- Wu Jian Department of Pharmacology, University of California at San Diego, 9500 Gilman Dr., 92093-0654, La Jolla, CA, USA aut NATIONALLICENCE 700 1- Taylor Susan Department of Pharmacology, University of California at San Diego, 9500 Gilman Dr., 92093-0654, La Jolla, CA, USA aut NATIONALLICENCE 773 0- Biophysical Reviews Springer Berlin Heidelberg 7/2(2015-06-01), 227-238 1867-2450 7:2<227 2015 7 12551