Phosphorylation of threonine 1736 in the C-terminal tail of integrin β4 contributes to hemidesmosome disassembly.

Molecular Biology of the Cell
Evelyne FrijnsArnoud Sonnenberg

Abstract

During wound healing, hemidesmome disassembly enables keratinocyte migration and proliferation. Hemidesmosome dynamics are altered downstream of epidermal growth factor (EGF) receptor activation, following the phosphorylation of integrin β4 residues S1356 and S1364, which reduces the interaction with plectin; however, this event is insufficient to drive complete hemidesmome disassembly. In the studies reported here, we used a fluorescence resonance energy transfer-based assay to demonstrate that the connecting segment and carboxy-terminal tail of the β4 cytoplasmic domain interact, which facilitates the formation of a binding platform for plectin. In addition, analysis of a β4 mutant containing a phosphomimicking aspartic acid residue at T1736 in the C-tail suggests that phosphorylation of this residue regulates the interaction with the plectin plakin domain. The aspartic acid mutation of β4 T1736 impaired hemidesmosome formation in junctional epidermolysis associated with pyloric atresia/β4 keratinocytes. Furthermore, we show that T1736 is phosphorylated downstream of protein kinase C and EGF receptor activation and is a substrate for protein kinase D1 in vitro and in cells, which requires its translocation to the plasma membr...Continue Reading

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Citations

Jun 12, 2013·Histochemistry and Cell Biology·Maria J CastañónGerhard Wiche
Aug 7, 2012·The Journal of Biological Chemistry·Trinayan Kashyap, Isaac Rabinovitz
Oct 25, 2012·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Martin J SiemerinkReinier O Schlingemann
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Dec 3, 2014·Current Opinion in Cell Biology·Naël Osmani, Michel Labouesse
Apr 8, 2015·Acta Crystallographica. Section D, Biological Crystallography·Noelia Alonso-GarcíaJosé M de Pereda
Nov 19, 2015·PloS One·Lisa Te Molder, Arnoud Sonnenberg
Aug 27, 2016·Matrix Biology : Journal of the International Society for Matrix Biology·Veronika RamovsArnoud Sonnenberg
Jul 6, 2017·Cancers·Yoshinobu KariyaJianguo Gu
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May 22, 2019·Cancers·Elisabete Cruz da SilvaMaxime Lehmann
Jun 22, 2012·Journal of Cell Science·Emilie FaureMaxime Lehmann
Sep 16, 2021·Journal of Cell Science·Lisa Te MolderArnoud Sonnenberg

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Methods Mentioned

BETA
two-hybrid
FRET
FCS
coIP
PMA
confocal microscopy
dot blot
transfection
PCR

Software Mentioned

FLIM
Li
Visual Basic
Netphos
Venus
ImageJ
ClustalW

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