Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/82738
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | The C-terminal domain of Mnk1a plays a dual role in tightly regulating its activity |
Author: | Goto, S. Yao, Z. Proud, C. |
Citation: | Biochemical Journal, 2009; 423(2):279-290 |
Publisher: | Portland Press |
Issue Date: | 2009 |
ISSN: | 0264-6021 1470-8728 |
Statement of Responsibility: | Susan Goto, Zhong Yao and Christopher G. Proud |
Abstract: | The human family of MAPK (mitogen-activated protein kinase) signal-integrating kinases (Mnks) comprises four related proteins derived from two genes by alternative splicing. The MNK1 gene gives rise to two proteins, Mnk1a and Mnk1b, which possess distinct C-termini and properties. Despite lacking the C-terminal MAPK-binding site, Mnk1b shows higher basal activity than Mnk1a. In contrast, the activity of Mnk1a is tightly regulated by signalling through ERK (extracellular-signal-regulated kinase) and p38 MAPK. We show that the short C-terminus of Mnk1b confers on it a ‘default’ behaviour of substantial, but unregulated, activity. In contrast, the longer C-terminus of Mnk1a represses the basal activity and T (activation)-loop phosphorylation of this isoenzyme while allowing both properties to be stimulated by upstream MAPK signalling. Two features of the C-terminus of Mnk1a appear to account for this behaviour: the known MAPK-binding site and a region (predicted to be α-helical) which occludes access to the catalytic domain and the T-loop. The activation of Mnk1a results in a marked conformational change leading to a more ‘open’ structure. We also identified a conserved phenylalanine residue in an Mnk-specific insert as playing a key role in governing the ease with which Mnk1a can be phosphorylated. These studies help to identify the features that give rise to the diverse properties of human Mnk isoforms. |
Keywords: | eukaryotic initiation factor 4E (eIF4E) extracellular-signal-regulated kinase (ERK) mitogen-activated protein kinase signal-integrating kinase (Mnk) p38 mitogen-activated protein kinase (p38 MAPK) protein kinase |
Rights: | © The Authors |
DOI: | 10.1042/BJ20090228 |
Published version: | http://dx.doi.org/10.1042/bj20090228 |
Appears in Collections: | Aurora harvest Molecular and Biomedical Science publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.