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Ssp2 Binding Activates the Smk1 Mitogen-Activated Protein Kinase
Chong Wai Tio1, Gregory Omerza1, Timothy Phillips1
1Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Molecular and Cellular Biology
|February 23, 2017
Summary
Smk1, a meiosis-specific kinase, requires binding to Ssp2 for activation. This binding, along with phosphorylation, enhances its catalytic activity and modifies its substrate specificity, revealing a novel activation mechanism for MAPKs.
Area of Science:
- Cellular Biology
- Molecular Biology
- Biochemistry
Background:
- Smk1 is a meiosis-specific mitogen-activated protein kinase (MAPK) in Saccharomyces cerevisiae.
- MAPK activation typically involves phosphorylation in the activation loop by a MAPK kinase.
- Smk1 activation deviates from this norm, involving cyclin-dependent kinase Cak1 and the meiosis-specific protein Ssp2.
Purpose of the Study:
- To elucidate the novel activation mechanism of the meiosis-specific MAPK, Smk1.
- To investigate the roles of Ssp2 binding and activation loop phosphorylation in Smk1 activity.
- To characterize the impact of Ssp2 on Smk1's catalytic function and substrate specificity.
Main Methods:
- In vitro kinase assays to assess Smk1 activity.
- Analysis of Smk1 phosphorylation sites (T207 and Y209).
- Investigating the interaction between Smk1 and Ssp2.
Main Results:
- Smk1 is catalytically inert without Ssp2 binding, which acts as an activator independent of activation loop phosphorylation.
- Ssp2 binding triggers autophosphorylation of Y209, and combined with T207 phosphorylation by Cak1, further enhances Smk1 activity.
- Smk1's substrate specificity is altered by Y209 autophosphorylation, enhancing S/T kinase activity and suppressing Y kinase activity.
Conclusions:
- A novel MAPK activation mechanism requiring direct activator binding (Ssp2) is defined.
- MAPK diversification allows recognition of unique phosphorylation motifs.
- This study expands the understanding of MAPK regulation and function in meiosis.
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