TY - JOUR
T1 - Solution structure of ERK2 binding domain of MAPK phosphatase MKP-3
T2 - Structural insights into MKP-3 activation by ERK2
AU - Farooq, Amjad
AU - Chaturvedi, Gaurav
AU - Mujtaba, Shiraz
AU - Plotnikova, Olga
AU - Zeng, Lei
AU - Dhalluin, Christophe
AU - Ashton, Robert
AU - Zhou, Ming Ming
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - MAP kinases (MAPKs), which control mitogenic signal transduction in all eukaryotic organisms, are inactivated by dual specificity MAPK phosphatases (MKPs). MKP-3, a prototypical MKP, achieves substrate specificity through its N-terminal domain binding to the MAPK ERK2, resulting in the activation of its C-terminal phosphatase domain. The solution structure and biochemical analysis of the ERK2 binding (EB) domain of MKP-3 show that regions that are essential for ERK2 binding partly overlap with its sites that interact with the C-terminal catalytic domain, and that these interactions are functionally coupled to the active site residues of MKP-3. Our findings suggest a novel mechanism by which the EB domain binding to ERK2 is transduced to cause a conformational change of the C-terminal catalytic domain, resulting in the enzymatic activation of MKP-3.
AB - MAP kinases (MAPKs), which control mitogenic signal transduction in all eukaryotic organisms, are inactivated by dual specificity MAPK phosphatases (MKPs). MKP-3, a prototypical MKP, achieves substrate specificity through its N-terminal domain binding to the MAPK ERK2, resulting in the activation of its C-terminal phosphatase domain. The solution structure and biochemical analysis of the ERK2 binding (EB) domain of MKP-3 show that regions that are essential for ERK2 binding partly overlap with its sites that interact with the C-terminal catalytic domain, and that these interactions are functionally coupled to the active site residues of MKP-3. Our findings suggest a novel mechanism by which the EB domain binding to ERK2 is transduced to cause a conformational change of the C-terminal catalytic domain, resulting in the enzymatic activation of MKP-3.
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U2 - 10.1016/S1097-2765(01)00186-1
DO - 10.1016/S1097-2765(01)00186-1
M3 - Article
C2 - 11239467
AN - SCOPUS:0035106342
VL - 7
SP - 387
EP - 399
JO - Molecular Cell
JF - Molecular Cell
SN - 1097-2765
IS - 2
ER -