James-Arroyo, Rafael and Lara-Rojas, Fernando and Bayram, Ozgur and Valerius, Oliver and Braus, Gerhard H. and Aguirrea, Jesus (2015) The SrkA Kinase Is Part of the SakA Mitogen-Activated Protein Kinase Interactome and Regulates Stress Responses and Development in Aspergillus nidulans. Eukaryotic Cell, 14 (5). pp. 295-510. ISSN 1535-9778

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Abstract

Fungi and many other eukaryotes use specialized mitogen-activated protein kinases (MAPK) of the Hog1/p38 family to transduce environmental stress signals. In Aspergillus nidulans, the MAPK SakA and the transcription factor AtfA are components of a central multiple stress-signaling pathway that also regulates development. Here we characterize SrkA, a putative MAPK-activated protein kinase, as a novel component of this pathway. ΔsrkA and ΔsakA mutants share a derepressed sexual development phenotype. However, ΔsrkA mutants are not sensitive to oxidative stress, and in fact, srkA inactivation partially suppresses the sensitivity of ΔsakA mutant conidia to H2O2, tert-butyl-hydroperoxide (t-BOOH), and menadione. In the absence of stress, SrkA shows physical interaction with nonphosphorylated SakA in the cytosol. We show that H2O2 induces a drastic change in mitochondrial morphology consistent with a fission process and the relocalization of SrkA to nuclei and mitochondria, depending on the presence of SakA. SakA-SrkA nuclear interaction is also observed during normal asexual development in dormant spores. Using SakA and SrkA S-tag pulldown and purification studies coupled to mass spectrometry, we found that SakA interacts with SrkA, the stress MAPK MpkC, the PPT1-type phosphatase AN6892, and other proteins involved in cell cycle regulation, DNA damage response, mRNA stability and protein synthesis, mitochondrial function, and other stress-related responses. We propose that oxidative stress induces DNA damage and mitochondrial fission and that SakA and SrkA mediate cell cycle arrest and regulate mitochondrial function during stress. Our results provide new insights into the mechanisms by which SakA and SrkA regulate the remodelling of cell physiology during oxidative stress and development.

Item Type:	Article
Additional Information:	The published version of this article is available at DOI: 10.1128/EC.00277-14. Supplemental material for this article may be found at http://dx.doi.org/10.1128 /EC.00277-14. Copyright © 2015, American Society for Microbiology.
Keywords:	SrkA Kinase; SakA Mitogen-Activated Protein; Kinase Interactome; Stress Responses; Development; Aspergillus nidulans;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	6583
Identification Number:	https://doi.org/10.1128/EC.00277-14.
Depositing User:	Ozgur Bayram
Date Deposited:	27 Nov 2015 16:16
Journal or Publication Title:	Eukaryotic Cell
Publisher:	American Society for Microbiology
Refereed:	Yes
URI:	http://ec.asm.org/
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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