Cyclic nucleotide-dependent protein kinases inhibit binding of 14-3-3 to the GTPase-activating protein Rap1GAP2 in platelets
- 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.
Verfasserangaben: | Meike HoffmeisterORCiDGND, Pavel Riha, Olga NeumüllerGND, Oliver DanielewskiGND, Jan SchultessGND, Albert SmolenskiORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-763593 |
DOI: | https://doi.org/10.1074/jbc.M706825200 |
ISSN: | 0021-9258 |
Pubmed-Id: | https://pubmed.ncbi.nlm.nih.gov/18039662 |
Titel des übergeordneten Werkes (Englisch): | Journal of biological chemistry |
Verlag: | American Society for Biochemistry and Molecular Biology Publications |
Verlagsort: | Bethesda, Md |
Dokumentart: | Wissenschaftlicher Artikel |
Sprache: | Englisch |
Datum der Veröffentlichung (online): | 04.01.2021 |
Jahr der Erstveröffentlichung: | 2008 |
Veröffentlichende Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Datum der Freischaltung: | 29.04.2024 |
Jahrgang: | 283.2008 |
Ausgabe / Heft: | 4 |
Seitenzahl: | 10 |
Erste Seite: | 2297 |
Letzte Seite: | 2306 |
Institute: | Medizin |
DDC-Klassifikation: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit | |
Sammlungen: | Universitätspublikationen |
Lizenz (Deutsch): | Creative Commons - CC BY - Namensnennung 4.0 International |