scholarly journals Serine/Threonine Protein Phosphatase 2B Catalytic Subunit Beta Isoform

2020 ◽  
Author(s):  
Keyword(s):  
Protein Phosphatase ◽  
Catalytic Subunit ◽  
Protein Phosphatase 2B

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 The catalytic subunit of protein phosphatase 2A is carboxyl-methylated in vivo.

1994 ◽  
Vol 269 (23) ◽  
pp. 16311-16317 ◽  
Author(s):  
B. Favre ◽  
S. Zolnierowicz ◽  
P. Turowski ◽  
B.A. Hemmings
Keyword(s):  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Catalytic Subunit ◽  
Phosphatase 2A

scholarly journals The split protein phosphatase system

2018 ◽  
Vol 475 (23) ◽  
pp. 3707-3723 ◽  
Author(s):  
Anne Bertolotti
Keyword(s):  
Protein Phosphatase ◽  
Catalytic Subunit ◽  
Regulatory Subunit ◽  
Post Translational Modification ◽  
Antagonistic Action ◽  
Cellular Processes ◽  
Depth Study ◽  
Split Protein ◽  
Phosphatase System ◽  
Physiological Substrates

Reversible phosphorylation of proteins is a post-translational modification that regulates all aspect of life through the antagonistic action of kinases and phosphatases. Protein kinases are well characterized, but protein phosphatases have been relatively neglected. Protein phosphatase 1 (PP1) catalyzes the dephosphorylation of a major fraction of phospho-serines and phospho-threonines in cells and thereby controls a broad range of cellular processes. In this review, I will discuss how phosphatases were discovered, how the view that they were unselective emerged and how recent findings have revealed their exquisite selectivity. Unlike kinases, PP1 phosphatases are obligatory heteromers composed of a catalytic subunit bound to one (or two) non-catalytic subunit(s). Based on an in-depth study of two holophosphatases, I propose the following: selective dephosphorylation depends on the assembly of two components, the catalytic subunit and the non-catalytic subunit, which serves as a high-affinity substrate receptor. Because functional complementation of the two modules is required to produce a selective holophosphatase, one can consider that they are split enzymes. The non-catalytic subunit was often referred to as a regulatory subunit, but it is, in fact, an essential component of the holoenzyme. In this model, a phosphatase and its array of mostly orphan substrate receptors constitute the split protein phosphatase system. The set of potentially generalizable principles outlined in this review may facilitate the study of these poorly understood enzymes and the identification of their physiological substrates.

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