1887

Abstract

Mitogen-activated protein kinase (MAPK) regulation of cAMP-specific phosphodiesterase function has been demonstrated in mammalian cells and suspected to occur in other eukaryotes. Epistasis analysis in the soil amoeba suggests the atypical MAPK Erk2 downregulates the function of the cAMP-specific phosphodiesterase RegA to regulate progression of the developmental life cycle. A putative MAPK docking motif located near a predicted MAPK phosphorylation site was characterized for contributions to RegA function and binding to Erk2 because a similar docking motif has been previously characterized in the mammalian PDE4D phosphodiesterase. The overexpression of RegA with alterations to this docking motif (RegA) restored RegA function to cells based on developmental phenotypes, but low-level expression of RegA from the endogenous promoter failed to rescue wild-type morphogenesis. Co-immunoprecipitation analysis indicated that Erk2 associates with both RegA and RegA, suggesting the docking motif is not required for this association. Epistasis analysis between and the only other MAPK, , suggests Erk1 and RegA can function in different pathways but that some phenotypes may require cAMP signalling. These results imply that MAPK downregulation of RegA in is accomplished through a different mechanism than MAPK regulation of cAMP-specific phosphodiesterases in mammalian cells and that the regulation in does not require a proximal MAPK docking motif.

Funding
This study was supported by the:
  • Oklahoma Center for the Advancement of Science and Technology (Award HR13-36)
    • Principle Award Recipient: Jeffrey A Hadwiger
  • National Institute of General Medical Sciences (Award NIGMS R15 GM097717-01)
    • Principle Award Recipient: Jeffrey A Hadwiger
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2019-11-15
2024-12-10
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