Kindlin-1 Regulates Epidermal Growth Factor Receptor Signaling.

Michael, Magdalene ORCID: 0000-0003-2577-729X, Begum, Rumena, Chan, Grace K ORCID: 0000-0002-7163-8285, Whitewood, Austin J ORCID: 0000-0002-8255-8248, Matthews, Daniel R, Goult, Benjamin T ORCID: 0000-0002-3438-2807, McGrath, John A ORCID: 0000-0002-3708-9964 and Parsons, Maddy ORCID: 0000-0002-2021-8379 (2019) Kindlin-1 Regulates Epidermal Growth Factor Receptor Signaling. The Journal of investigative dermatology, 139 (2). pp. 369-379.

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Official URL: http://dx.doi.org/10.1016/j.jid.2018.08.020

Abstract

Kindler syndrome is an autosomal recessive genodermatosis that results from mutations in the FERMT1 gene encoding t kindlin-1. Kindlin-1 localizes to focal adhesion and is known to contribute to the activation of integrin receptors. Most cases of Kindler syndrome 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 this study we show that skin and keratinocytes from Kindler syndrome patients have significantly reduced expression levels of the EGFR, resulting in defective EGF-dependent signaling and cell migration. Mechanistically, we show 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 show that kindlin-1 acts to protect EGFR from lysosomal-mediated degradation. This shows a new role for kindlin-1 that has implications for understanding Kindler syndrome disease pathology.

Item Type:	Article
Uncontrolled Keywords:	Cell Line, Lysosomes, Keratinocytes, Skin, Humans, Periodontal Diseases, Epidermolysis Bullosa, Photosensitivity Disorders, Blister, Membrane Proteins, Neoplasm Proteins, Signal Transduction, Cell Movement, Proteolysis, EGF Family of Proteins, ErbB Receptors
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	13 Mar 2024 09:57
Last Modified:	13 Mar 2024 09:57
DOI:	10.1016/j.jid.2018.08.020
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3179315