Phosphorylation of protein S by platelet kinases enhances its activated protein C cofactor activity
| Autor: | Andrew J. Gale, Mary J. Heeb, Fabian Stavenuiter |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Blood Platelets
Models Molecular Threonine animal structures Immunoblotting Molecular Sequence Data Peptide Biochemistry Mass Spectrometry Protein S Research Communications Genetics medicine Humans Amino Acid Sequence Platelet activation Phosphorylation Casein Kinase II Molecular Biology chemistry.chemical_classification Binding Sites Sequence Homology Amino Acid biology Casein Kinase I Kinase Imidazoles Protein Structure Tertiary Enzyme Activation chemistry Benzamides biology.protein Partial Thromboplastin Time Casein kinase 1 Casein kinase 2 Oligopeptides Protein Kinases Protein C Biotechnology medicine.drug |
| Zdroj: | The FASEB Journal. 27:2918-2925 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.12-225961 |
| Popis: | Protein S (PS) is a multifunctional plasma protein of the hemostatic and inflammatory pathways, although mechanisms for its regulation are poorly understood. Since certain plasma proteins are regulated through extracellular phosphorylation, we investigated whether the anticoagulant activity of PS is regulated through phosphorylation by platelet-secreted kinases. PS was phosphorylated on exposure to activated platelets or their releasates, as judged by immunoblotting for phospho-amino acids and PS. PS phosphorylation was reduced by specific inhibitors of casein kinase 1 (CK1) and casein kinase 2 (CK2) (10 μM D4476, 100 μM CK2-inhibitory peptide YNLKSKSSEDIDESS). Involvement of CKs in PS phosphorylation was confirmed using purified CK1/CK2. Phosphorylation of PS by purified CK1 did not affect its activated protein C (APC) cofactor activity in activated partial thromboplastin time assays in PS-depleted plasma. However, phosphorylation of PS by CK2 or by CK1/CK2 increased PS cofactor activity ∼1.5-fold (158.7±4.8%, P |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text