Functional role of three water molecules buried within catalytic subunit of cyclic 3′,5′-adenosine monophosphate-dependent protein kinase

2007 ◽  
Vol 809 (1-3) ◽  
pp. 21-27 ◽  
Author(s):  
Hai-Xiao Jin ◽  
Tian-Xing Wu ◽  
Yong-Jun Jiang ◽  
Jian-Wei Zou ◽  
Shu-Lin Zhuang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Functional Role ◽  
Adenosine Monophosphate ◽  
Catalytic Subunit ◽  
Water Molecules ◽  
Dependent Protein Kinase ◽  
Dependent Protein

Potent inhibition of human platelets by cGMP analogs independent of cGMP-dependent protein kinase

Blood ◽  
2004 ◽  
Vol 103 (7) ◽  
pp. 2593-2600 ◽  
Author(s):  
Stepan Gambaryan ◽  
Jörg Geiger ◽  
Ulrike R. Schwarz ◽  
Elke Butt ◽  
Antonija Begonja ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Platelet Activation ◽  
Vascular Function ◽  
Adenosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Dependent Protein Kinase ◽  
Cgmp Dependent Protein Kinase ◽  
Erk Phosphorylation ◽  
Dependent Protein

Abstract Platelets play a key role in hemostasis through their ability to rapidly adhere to activated or injured endothelium, subendothelial matrix proteins, and other activated platelets. A strong equilibrium between activating and inhibiting processes is essential for normal platelet and vascular function, impairment of this equilibrium being associated with either thrombophilic or bleeding disorders. Both cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) have been established as crucial and synergistic intracellular messengers that mediate the effects of platelet inhibitors such as nitric oxide (NO) and prostacyclin (PG-I2). However, it was recently suggested that a rapid cGMP/cGMP-dependent protein kinase (cGK)–mediated extracellular signal-related kinase (ERK) phosphorylation promotes platelet activation. This hypothesis was examined here by evaluating established and proposed cGK activators/inhibitors with respect to their capacity to promote either platelet activation or inhibition. In particular, the regulatory role of cGK for ERK phosphorylation and thrombin-, thromboxane-, and VWF-induced platelet activation was investigated. The data obtained do not support the concept that cGK-mediated ERK phosphorylation promotes platelet activation but confirm the inhibitory role of cGK in platelet function. One explanation for these discrepancies is the novel finding that extracellular cGMP analogs potently and rapidly inhibit thrombin-, thromboxane-, and VWF-induced human platelet signaling and activation by a cGK-independent mechanism.

Role of phosphorylated Thr-197 in the catalytic subunit of cAMP-dependent protein kinase

2007 ◽  
Vol 805 (1-3) ◽  
pp. 9-15 ◽  
Author(s):  
Hai-Xiao Jin ◽  
Tian-Xing Wu ◽  
Yong-Jun Jiang ◽  
Jian-Wei Zou ◽  
Shu-Lin Zhuang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Catalytic Subunit ◽  
Dependent Protein Kinase ◽  
Camp Dependent Protein Kinase ◽  
Dependent Protein
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