TheSaccharomyces cerevisiae genes (CMP1 andCMP2) encoding calmodulin-binding proteins homologous to the catalytic subunit of mammalian protein phosphatase 2B

1991 ◽  
Vol 227 (1) ◽  
pp. 52-59 ◽  
Author(s):  
Yusen Liu ◽  
Satoru Ishii ◽  
Masaya Tokai ◽  
Hiroko Tsutsumi ◽  
Osamu Ohki ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Binding Proteins ◽  
Catalytic Subunit ◽  
Calmodulin Binding ◽  
Protein Phosphatase 2B ◽  
Mammalian Protein

Suppression of Murine Platelet Activation by the β Isoform of the Catalytic Subunit of Protein Phosphatase 2B

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 190-190
Author(s):  
Francisca C. Gushiken ◽  
Nawaf Alrehani ◽  
Subhashree Pradhan ◽  
Lavanya Kailasam ◽  
Rolando Rumbaut ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Protein Phosphatase ◽  
Conflicts Of Interest ◽  
Fibrin Clot ◽  
Catalytic Subunit ◽  
Low Doses ◽  
Clot Retraction ◽  
Protein Phosphatase 2B ◽  
Platelet Functions

Abstract Abstract 190 Signal transduction mediated by the kinases and phosphatases are critical for platelet activation at the site of vascular injury. Compared to the kinases, a role for phosphatases in platelet activation is less understood. Our previous studies have focused on the roles of serine/threonine protein phosphatase 1 (PP1) and 2A (PP2A) in regulating integrin αIIbβ3functions. However, platelets also express protein phosphatase 2B (PP2B) and its role in platelet function is unexplored. PP2B-Aα and PP2B-Aβ constitute two ubiquitous isoforms of the PP2B catalytic subunit. Due to the general concerns regarding the specificity of the PP2B inhibitors, we have utilized mice deficient in the β isoform of the catalytic subunit of PP2B (PP2B-Aβ) to explore the role of PP2B in platelet functions. Mice lacking PP2B-Aα are short lived and are not considered in this study. Loss of PP2B-Aβ did not cause any compensatory increase in the PP2B-Aα levels in platelets. Compared to the wild type (WT) platelets, PP2B-Aβ−/− platelets displayed increased aggregation in response to low doses of protease-activated receptor 4-activating peptide (PAR4-AP), ADP, collagen and collagen related peptide (CRP). Enhanced α granule secretion in response to the low doses of PAR4-AP and CRP was noticed in PP2B-Aβ−/− platelets, relative to the WT platelets. Functions regulated by the outside-in αIIbβ3 integrin signaling like adhesion to immobilized fibrinogen and fibrin clot retraction were enhanced in the PP2B-Aβ−/− platelets. These studies indicate that PP2B-Aβ negatively regulate platelet functions in vitro. Consistent with these observations, PP2B-Aβ−/− mice exhibited a shorter tail bleeding time compared to the WT mice. In a FeCl3 induced endothelial denudation injury model, PP2B-Aβ−/− mice showed decreased time to occlusion in the carotid artery, and reduced number of emboli compared to the WT mice. These studies indicate that PP2B-Aβ suppress multiple murine platelet functions that contribute to an occlusive thrombi. Unlike a positive thrombus promoting role for the PP1cγ that was noticed in our previous study, PP2B-Aβ suppressed murine platelet activation, suggesting that different subtypes of Ser/Thr phosphatases have distinct roles in murine platelet activation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Importance of the β12-β13 Loop in Protein Phosphatase-1 Catalytic Subunit for Inhibition by Toxins and Mammalian Protein Inhibitors

1999 ◽  
Vol 274 (32) ◽  
pp. 22366-22372 ◽  
Author(s):  
John H. Connor ◽  
Theresa Kleeman ◽  
Sailen Barik ◽  
Richard E. Honkanen ◽  
Shirish Shenolikar
Keyword(s):  
Protein Phosphatase ◽  
Catalytic Subunit ◽  
Protein Phosphatase 1 ◽  
Protein Inhibitors ◽  
Mammalian Protein
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