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Elife. 2017 Apr 21;6. pii: e22759. doi: 10.7554/eLife.22759.

Ezrin activation by LOK phosphorylation involves a PIP2-dependent wedge mechanism.

Author information

1
Weill Institute for Molecular and Cell Biology, Cornell University, Ithaca, United States.
2
Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States.
3
Department of Genetics, Harvard Medical School, Boston, United States.

Abstract

How cells specify morphologically distinct plasma membrane domains is poorly understood. Prior work has shown that restriction of microvilli to the apical aspect of epithelial cells requires the localized activation of the membrane-F-actin linking protein ezrin. Using an in vitro system, we now define a multi-step process whereby the kinase LOK specifically phosphorylates ezrin to activate it. Binding of PIP2 to ezrin induces a conformational change permitting the insertion of the LOK C-terminal domain to wedge apart the membrane and F-actin-binding domains of ezrin. The N-terminal LOK kinase domain can then access a site 40 residues distal from the consensus sequence that collectively direct phosphorylation of the appropriate threonine residue. We suggest that this elaborate mechanism ensures that ezrin is only phosphorylated at the plasma membrane, and with high specificity by the apically localized kinase LOK.

KEYWORDS:

Cell polarity; Ezrin; LOK; Microvilli; SLK; biochemistry; cell biology; human

PMID:
28430576
PMCID:
PMC5400502
DOI:
10.7554/eLife.22759
[Indexed for MEDLINE]
Free PMC Article

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