What question did this study set out to answer?

To identify the specific serine residues and kinase pathways responsible for integrin β4 phosphorylation during hemidesmosome disassembly and keratinocyte migration.

September 25, 2010Journal of Biological ChemistryOpen Access

EGF-induced MAPK Signaling Inhibits Hemidesmosome Formation through Phosphorylation of the Integrin β4

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Authors

EFEvelyne FrijnsAstraZeneca (Switzerland)NSNorman SachsRoyal Netherlands Academy of Arts and Sciences MKMaaike KreftDutch Cancer Society

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Implication

In vitro study reveals that EGF-activated MAPK signaling disrupts hemidesmosome stability in keratinocytes, indicating a key mechanism governing epithelial cell motility.

Key Points

To identify the specific serine residues and kinase pathways responsible for integrin β4 phosphorylation during hemidesmosome disassembly and keratinocyte migration.
Stimulated keratinocytes with PMA or EGF to assess phosphorylation events on specific serine residues of the integrin β4 cytoplasmic domain.
Identified mediating kinases using pathway analyses and tested interactions using phospho-mimicking aspartic acid mutations at Ser-1356 and Ser-1364.
Evaluated keratinocyte motility, hemidesmosome stability, plectin binding, and α6β4-mediated adhesion to laminin-332 during migration and mitotic cell rounding.
Stimulation with PMA or EGF induced phosphorylation of integrin β4 selectively at Ser-1356 and Ser-1364 via ERK1/2 and downstream p90RSK1/2, rather than PKC.
Phospho-mimicking mutations at Ser-1356 and Ser-1364 reduced integrin β4 binding to plectin and weakened α6β4-mediated adhesion to laminin-332.
EGF-induced phosphorylation reduced stable hemidesmosome assembly while accelerating keratinocyte migration, whereas mitotic cell rounding triggered phosphorylation exclusively at Ser-1356.

Cite This Study

Frijns et al. (2010) studied this question.

synapsesocial.com/papers/6a87eafa8a3f93fc1e062b83 https://doi.org/10.1074/jbc.m110.138818

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Implication

In vitro study reveals that EGF-activated MAPK signaling disrupts hemidesmosome stability in keratinocytes, indicating a key mechanism governing epithelial cell motility.

EGF-induced MAPK Signaling Inhibits Hemidesmosome Formation through Phosphorylation of the Integrin β4

Discussion

Member takes

Implication

Key Points

Cite This Study

EGF-induced MAPK Signaling Inhibits Hemidesmosome Formation through Phosphorylation of the Integrin β4

Discussion

Member takes

Implication

Key Points

Cite This Study

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