The Phosphorylation State of Threonine-220, a Uniquely Phosphatase-Sensitive Protein Kinase A Site in Microtubule-Associated Protein MAP2c, Regulates Microtubule Binding and Stability†

Biochemistry ◽  
2002 ◽  
Vol 41 (41) ◽  
pp. 12427-12435 ◽  
Author(s):  
A. Alexa ◽  
G. Schmidt ◽  
P. Tompa ◽  
S. Ogueta ◽  
J. Vázquez ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Microtubule Binding ◽  
Phosphorylation State ◽  
A Site ◽  
Kinase A

scholarly journals Protein Kinase A Site-specific Phosphorylation Regulates ATP-binding Cassette A1 (ABCA1)-mediated Phospholipid Efflux

2002 ◽  
Vol 277 (44) ◽  
pp. 41835-41842 ◽  
Author(s):  
Raymond H. See ◽  
Rosalinda A. Caday-Malcolm ◽  
Roshni R. Singaraja ◽  
Steven Zhou ◽  
Anthony Silverston ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Atp Binding ◽  
Site Specific ◽  
A Site ◽  
Kinase A ◽  
Atp Binding Cassette

scholarly journals Unidirectional allostery in the regulatory subunit RIα facilitates efficient deactivation of protein kinase A

2016 ◽  
Vol 113 (44) ◽  
pp. E6776-E6785 ◽  
Author(s):  
Cong Guo ◽  
Huan-Xiang Zhou
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Structural Similarity ◽  
Community Analysis ◽  
Catalytic Subunit ◽  
Regulatory Subunit ◽  
Allosteric Communication ◽  
Dynamics Simulations ◽  
A Site ◽  
Kinase A

The holoenzyme complex of protein kinase A is in an inactive state; activation involves ordered cAMP binding to two tandem domains of the regulatory subunit and release of the catalytic subunit. Deactivation has been less studied, during which the two cAMPs unbind from the regulatory subunit to allow association of the catalytic subunit to reform the holoenzyme complex. Unbinding of the cAMPs appears ordered as indicated by a large difference in unbinding rates from the two sites, but the cause has remained elusive given the structural similarity of the two tandem domains. Even more intriguingly, NMR data show that allosteric communication between the two domains is unidirectional. Here, we present a mechanism for the unidirectionality, developed from extensive molecular dynamics simulations of the tandem domains in different cAMP-bound forms. Disparate responses to cAMP releases from the two sites (A and B) in conformational flexibility and chemical shift perturbation confirmed unidirectional allosteric communication. Community analysis revealed that the A-site cAMP, by forming across-domain interactions, bridges an essential pathway for interdomain communication. The pathway is impaired when this cAMP is removed but remains intact when only the B-site cAMP is removed. Specifically, removal of the A-site cAMP leads to the separation of the two domains, creating room for binding the catalytic subunit. Moreover, the A-site cAMP, by maintaining interdomain coupling, retards the unbinding of the B-site cAMP and stalls an unproductive pathway of cAMP release. Our work expands the perspective on allostery and implicates functional importance for the directionality of allostery.

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