Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 387-399 |
| Number of pages | 13 |
| Journal | Molecular Cell |
| Volume | 7 |
| Issue number | 2 |
| DOIs | |
| State | Published - Mar 22 2001 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Molecular Biology
Cite this
Solution structure of ERK2 binding domain of MAPK phosphatase MKP-3 : Structural insights into MKP-3 activation by ERK2. / Farooq, Amjad; Chaturvedi, Gaurav; Mujtaba, Shiraz; Plotnikova, Olga; Zeng, Lei; Dhalluin, Christophe; Ashton, Robert; Zhou, Ming Ming.
In: Molecular Cell, Vol. 7, No. 2, 22.03.2001, p. 387-399.Research output: Contribution to journal › Article
}
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
PY - 2001/3/22
Y1 - 2001/3/22
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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UR - http://www.scopus.com/inward/citedby.url?scp=0035106342&partnerID=8YFLogxK
U2 - 10.1016/S1097-2765(01)00186-1
DO - 10.1016/S1097-2765(01)00186-1
M3 - Article
VL - 7
SP - 387
EP - 399
JO - Molecular Cell
JF - Molecular Cell
SN - 1097-2765
IS - 2
ER -