The EF2K/MHCK/TRPM7 family of atypical protein kinases

Shari L. Wiseman, Fan Yan Wei, Angus C. Nairn

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

Abstract

The crystal structure of the catalytic domain of TRPM7 has provided insight into enzymatic function of the EF2K/MHCK/TRPM7 atypical kinase family. The kinase domain of TRPM7 forms a dimer as a consequence of a "domain swapping" exchange of an N-terminal 27-residue "dimerization segment." Substantial evidence indicates that EF2K is highly regulated by second messengers, in particular Ca2+, and serves to integrate the effects of multiple signaling pathways on the regulation of protein synthesis. Phosphorylation of EF2 results in inhibition of the elongation step of protein synthesis, and therefore activation of EF2K by Ca2+/calmodulin inversely couples the level of intracellular Ca2+ to the overall rate of protein synthesis. EF2K activity is regulated both positively and negatively downstream of metabolic and cellular stress pathways. EF2K plays a role in the activity-dependent regulation of "local protein synthesis" in specific subcellular compartments. Phosphorylation of EF2 in dendrites is bidirectionally regulated by local modulation of miniature synaptic transmission, while depolarization of neuronal growth cones has been found to increase EF2 phosphorylation. Phosphorylation of EF2 potently inhibits the elongation step of protein synthesis, possibly through reduction of its affinity for the ribosome. This EF2K-dependent regulation of translation in neurons has been implicated in the consolidation of new memories for long-term storage. EF2K may also play a role in certain disease states, most notably the dysregulation of protein synthesis involved in cancer.

Original languageEnglish
Title of host publicationHandbook of Cell Signaling, 2/e
PublisherElsevier Inc.
Pages587-599
Number of pages13
Volume2
ISBN (Print)9780123741455
DOIs
Publication statusPublished - 2010 Dec 1
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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