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Emerging roles of the protein kinase MK2 in spermatogenesis
Dissertation   Open access

Emerging roles of the protein kinase MK2 in spermatogenesis

Patrick Allen Williams
Doctor of Philosophy (Ph.D.), Drexel University
Jul 2017
DOI:
https://doi.org/10.17918/etd-7528
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Abstract

Molecular Biology
Developing male germ cells are highly sensitive to environmental stresses such as heat and oxidative damage. The inability of these cells to mitigate such insults often results in germ cell apoptosis, a decline in the number of functional sperm, and reduced fertility. Cells respond and recover from stress, in part, by activating specific intracellular signaling pathways. Foremost amongst these is the p38 MAP kinase (MAPK) pathway, a stress-induced signal transduction pathway with well-established roles in eliciting protective responses in many cell types exposed to damage. Upon activation, p38 phosphorylates and activates multiple substrates including the serine/threonine kinase MAPKAP kinase 2 (MK2); however, the precise role that MK2 plays in regulating spermatogenesis is unknown. In this work, we have identified two new germ cell-specific substrates of MK2, the RNA-binding protein Dazl (deleted in azoospermia-like) and HspA1L, a testis-specific heat shock protein of the Hsp70 family. We have determined the physiological functions of MK2-mediated phosphorylation of these proteins and the possible roles that these post-translational modifications may play in germ cell biology. These findings firmly establish a novel role for this kinase in regulating the stress response in developing male germ cells. Moreover, our results lend support to a model in which spatiotemporal activation of MK2 may either promote or inhibit the process of spermatogenesis in response to stress.

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