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Kindlin-1 regulates epidermal growth factor receptor signalling

Michael, M., Begum, R., Chan, G.K., Whitewood, A.J., Matthews, D.R., Goult, Benjamin T., McGrath, J.A., Parsons, Maddy (2018) Kindlin-1 regulates epidermal growth factor receptor signalling. Journal of Investigative Dermatology, 139 . pp. 369-379. ISSN 0022-202X. (doi:10.1016/j.jid.2018.08.020) (KAR id:69218)

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Kindler syndrome (KS) is an autosomal recessive genodermatosis that results from mutations in the FERMT1 gene encoding kindlin-1. Kindlin-1 localises to focal adhesion and is known to contribute to the activation of integrin receptors. Most cases of KS show a reduction or complete absence of kindlin-1 in keratinocytes, resulting in defective integrin activation, cell adhesion and migration. However, roles for kindlin-1 beyond integrin activation remain poorly defined. In the current study we show that skin and keratinocytes from KS patients have significantly reduced expression levels of the epidermal growth factor receptor (EGFR), resulting in defective EGF-dependent signalling and cell migration. Mechanistically, we demonstrate that kindlin-1 can associate directly with EGFR in vitro and in keratinocytes in an EGF-dependent, integrin-independent manner and that formation of this complex is required for EGF-dependent migration. We further demonstrate that kindlin-1 acts to protect EGFR from lysosomal-mediated degradation. This reveals a new role for kindlin-1 that has implications for understanding KS disease pathology.

Item Type: Article
DOI/Identification number: 10.1016/j.jid.2018.08.020
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Ben Goult
Date Deposited: 23 Sep 2018 14:03 UTC
Last Modified: 28 Aug 2020 12:22 UTC
Resource URI: (The current URI for this page, for reference purposes)
Goult, Benjamin T.:
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