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https://hdl.handle.net/2440/82738
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dc.contributor.author | Goto, S. | - |
dc.contributor.author | Yao, Z. | - |
dc.contributor.author | Proud, C. | - |
dc.date.issued | 2009 | - |
dc.identifier.citation | Biochemical Journal, 2009; 423(2):279-290 | - |
dc.identifier.issn | 0264-6021 | - |
dc.identifier.issn | 1470-8728 | - |
dc.identifier.uri | http://hdl.handle.net/2440/82738 | - |
dc.description.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. | - |
dc.description.statementofresponsibility | Susan Goto, Zhong Yao and Christopher G. Proud | - |
dc.language.iso | en | - |
dc.publisher | Portland Press | - |
dc.rights | © The Authors | - |
dc.source.uri | http://dx.doi.org/10.1042/bj20090228 | - |
dc.subject | eukaryotic initiation factor 4E (eIF4E) | - |
dc.subject | extracellular-signal-regulated kinase (ERK) | - |
dc.subject | mitogen-activated protein kinase signal-integrating kinase (Mnk) | - |
dc.subject | p38 mitogen-activated protein kinase (p38 MAPK) | - |
dc.subject | protein kinase | - |
dc.title | The C-terminal domain of Mnk1a plays a dual role in tightly regulating its activity | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1042/BJ20090228 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Proud, C. [0000-0003-0704-6442] | - |
Appears in Collections: | Aurora harvest Molecular and Biomedical Science publications |
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