p38 Map Kinase Substrate Specificity Differs Greatly for Protein and Peptide Substrates

2000 ◽  
Vol 382 (2) ◽  
pp. 310-313 ◽  
Author(s):  
Julio Hawkins ◽  
Song Zheng ◽  
Betsy Frantz ◽  
Philip LoGrasso
Keyword(s):  
Substrate Specificity ◽  
Map Kinase ◽  
P38 Map Kinase ◽  
Peptide Substrates ◽  
Kinase Substrate

scholarly journals Cushing’s Syndrome mutant PKAL205R exhibits altered substrate specificity

2016 ◽  
Author(s):  
Joshua M. Lubner ◽  
Kimberly L. Dodge-Kafka ◽  
Cathrine R. Carlson ◽  
George M. Church ◽  
Michael F. Chou ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Cushing’S Syndrome ◽  
Cushing's Syndrome ◽  
Peptide Library ◽  
Loss Of Function ◽  
New Paradigm ◽  
Disease Etiology ◽  
Peptide Substrates ◽  
Kinase Substrate ◽  
High Resolution Models

AbstractThe PKAL205R hotspot mutation has been implicated in Cushing’s Syndrome through hyperactive gain-of-function PKA signaling, however its influence on substrate specificity has not been investigated. Here, we employ the Proteomic Peptide Library (ProPeL) approach to create high-resolution models for PKAWT and PKAL205R substrate specificity. We reveal that the L205R mutation reduces canonical hydrophobic preference at the substrate P+1 position, and increases acidic preference in downstream positions. Using these models, we designed peptide substrates that exhibit altered selectivity for specific PKA variants, and demonstrate the feasibility of selective PKAL205R loss-of-function signaling. Through these results, we suggest that substrate rewiring may contribute to Cushing’s Syndrome disease etiology, and introduce a powerful new paradigm for investigating mutation-induced kinase substrate rewiring in human disease.

Novel Homologues of CSBP/p38 MAP Kinase: Activation, Substrate Specificity and Sensitivity to Inhibition by Pyridinyl Imidazoles

1997 ◽  
Vol 235 (3) ◽  
pp. 533-538 ◽  
Author(s):  
Sanjay Kumar ◽  
Peter C. McDonnell ◽  
Rebecca J. Gum ◽  
Annalisa T. Hand ◽  
John C. Lee ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Map Kinase ◽  
P38 Map Kinase ◽  
Kinase Activation ◽  
Specificity And Sensitivity
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