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bioRxiv · 10.1101/828111

iTRAQ-based proteomic and phosphoproteomic analyses of STRIPAK mutants from the fungus Sordaria macrospora identifies a conserved serine phosphorylation site in PAK kinase CLA4 to be important for sexual development and polarized growth

Märker, R.·Blank-Landeshammer, B.·Beier-Rosberger, A.·Sickmann, A.·Kück, U.
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Abstract

The highly conserved striatin-interacting phosphatases and kinases (STRIPAK) complex regulates phosphorylation of developmental proteins in eukaryotic microorganisms, animals, and humans. To first identify potential targets of STRIPAK, we performed extensive isobaric tags for relative and absolute quantification (iTRAQ)-based proteomic and phosphoproteomic analyses in the filamentous fungus Sordaria macrospora. In total, we identified 4,193 proteins and 2,489 phosphoproteins, which are represented by 10,635 phosphopeptides. By comparing phosphorylation data from wild-type and mutants, we identified 228 phosphoproteins to be regulated in all three STRIPAK mutants, thus representing potential targets of STRIPAK. To provide an exemplarily functional analysis of a STRIPAK-dependent phosphorylated protein, we selected CLA4, a member of the conserved p21-activated kinase (PAK) family. Functional characterization of the {Delta}cla4 deletion strain showed that CLA4 controls sexual development and polarized growth. To determine the functional relevance of CLA4 phosphorylation and the impact of specific phosphorylation sites on development, we next generated phospho-mimetic and -deficient variants of CLA4. This analysis identified (de)phosphorylation of a highly conserved serine (S685) residue in the catalytic domain of CLA4 as being important for fungal cellular development. Collectively, these analyses significantly contribute to the understanding of the mechanistic function of STRIPAK as a phosphatase and kinase signaling complex.

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Märker, R., Blank-Landeshammer, B., Beier-Rosberger, A., Sickmann, A., Kück, U.. 2019-11-04. iTRAQ-based proteomic and phosphoproteomic analyses of STRIPAK mutants from the fungus Sordaria macrospora identifies a conserved serine phosphorylation site in PAK kinase CLA4 to be important for sexual development and polarized growth. https://doi.org/10.1101/828111

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