Universität zu Köln

Isensee, Joerg ORCID: 0000-0002-3390-0051, Kaufholz, Melanie, Knape, Matthias J., Hasenauer, Jan ORCID: 0000-0002-4935-3312, Hammerich, Hanna, Gonczarowska-Jorge, Humberto, Zahedi, Rene P., Schwede, Frank, Herberg, Friedrich W. and Hucho, Tim ORCID: 0000-0002-4147-9308 (2018). PKA-RII subunit phosphorylation precedes activation by cAMP and regulates activity termination. J. Cell Biol., 217 (6). S. 2167 - 2185. NEW YORK: ROCKEFELLER UNIV PRESS. ISSN 1540-8140

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Abstract

Type II isoforms of cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA-II) contain a phosphorylatable epitope within the inhibitory domain of RII subunits (pRII) with still unclear function. In vitro, RII phosphorylation occurs in the absence of cAMP, whereas staining of cells with pRII-specific antibodies revealed a cAMP-dependent pattern. In sensory neurons, we found that increased pRII immunoreactivity reflects increased accessibility of the already phosphorylated RII epitope during cAMP-induced opening of the tetrameric RII2:C-2 holoenzyme. Accordingly, induction of pRII by cAMP was sensitive to novel inhibitors of dissociation, whereas blocking catalytic activity was ineffective. Also in vitro, cAMP increased the binding of pRII antibodies to RII2:C-2 holoenzymes. Identification of an antibody specific for the glycine-rich loop of catalytic subunits facing the pRII-epitope confirmed activity-dependent binding with similar kinetics, proving that the reassociation is rapid and precisely controlled. Mechanistic modeling further supported that RII phosphorylation precedes cAMP binding and controls the inactivation by modulating the reassociation involving the coordinated action of phosphodiesterases and phosphatases.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Isensee, Joerg UNSPECIFIED orcid.org/0000-0002-3390-0051 UNSPECIFIED Kaufholz, Melanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Knape, Matthias J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hasenauer, Jan UNSPECIFIED orcid.org/0000-0002-4935-3312 UNSPECIFIED Hammerich, Hanna UNSPECIFIED UNSPECIFIED UNSPECIFIED Gonczarowska-Jorge, Humberto UNSPECIFIED UNSPECIFIED UNSPECIFIED Zahedi, Rene P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwede, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Herberg, Friedrich W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hucho, Tim UNSPECIFIED orcid.org/0000-0002-4147-9308 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-184210
DOI:	10.1083/jcb.201708053
Journal or Publication Title:	J. Cell Biol.
Volume:	217
Number:	6
Page Range:	S. 2167 - 2185
Date:	2018
Publisher:	ROCKEFELLER UNIV PRESS
Place of Publication:	NEW YORK
ISSN:	1540-8140
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DEPENDENT PROTEIN-KINASE; RESONANCE ENERGY-TRANSFER; RABBIT SKELETAL-MUSCLE; CATALYTIC SUBUNIT; ENZYME ACTIVATION; SENSORY NEURONS; TRANSFER BRET; ADENOSINE 3; A ACTIVITY; DYNAMICS Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/18421