TY  - JOUR
A1  - Hoffmeister, Meike
A1  - Riha, Pavel
A1  - Neumüller, Olga
A1  - Danielewski, Oliver
A1  - Schultess, Jan
A1  - Smolenski, Albert
T1  - Cyclic nucleotide-dependent protein kinases inhibit binding of 14-3-3 to the GTPase-activating protein Rap1GAP2 in platelets
T2  - Journal of biological chemistry
N2  - GTPase-activating proteins are required to terminate signaling by Rap1, a small guanine nucleotide-binding protein that controls integrin activity and cell adhesion. Recently, we identified Rap1GAP2, a GTPase-activating protein of Rap1 in platelets. Here we show that 14-3-3 proteins interact with phosphorylated serine 9 at the N terminus of Rap1GAP2. Platelet activation by ADP and thrombin enhances serine 9 phosphorylation and increases 14-3-3 binding to endogenous Rap1GAP2. Conversely, inhibition of platelets by endothelium-derived factors nitric oxide and prostacyclin disrupts 14-3-3 binding. These effects are mediated by cGMP- and cAMP-dependent protein kinases that phosphorylate Rap1GAP2 at serine 7, adjacent to the 14-3-3 binding site. 14-3-3 binding does not change the GTPase-activating function of Rap1GAP2 in vitro. However, 14-3-3 binding attenuates Rap1GAP2 mediated inhibition of cell adhesion. Our findings define a novel crossover point of activatory and inhibitory signaling pathways in platelets.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/76359
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-763593
SN  - 0021-9258
VL  - 283.2008
IS  - 4
SP  - 2297
EP  - 2306
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -