Kindlin-1 Regulates Epidermal Growth Factor Receptor Signaling
| Autor: | Magdalene, Michael, Rumena, Begum, Grace K, Chan, Austin J, Whitewood, Daniel R, Matthews, Benjamin T, Goult, John A, McGrath, Maddy, Parsons |
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| Rok vydání: | 2018 |
| Předmět: |
Keratinocytes
EGF Family of Proteins MST microscale thermophoresis Membrane Proteins IP immunoprecipitation KS Kindler syndrome FRET fluorescence resonance energy transfer Article Cell Line Neoplasm Proteins EGFR epidermal growth factor receptor ErbB Receptors Blister PBS phosphate buffered saline Cell Movement WT wild type Proteolysis Humans Photosensitivity Disorders Epidermolysis Bullosa Lysosomes Periodontal Diseases Signal Transduction Skin |
| Zdroj: | The Journal of Investigative Dermatology |
| ISSN: | 1523-1747 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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