A wound-induced keratin inhibits Src activity during keratinocyte migration and tissue repair

Jeremy D. Rotty, Pierre A. Coulombe

Research output: Contribution to journalArticle

Abstract

Injury to the epidermis triggers an elaborate homeostatic response resulting in tissue repair and recovery of the vital barrier function. The type II keratins 6a and 6b (K6a and K6b) are among the genes induced early on in wound-proximal keratinocytes and maintained during reepithelialization. Paradoxically, genetic ablation of K6a and K6b results in enhanced keratinocyte migration. In this paper, we show that this trait results from activation of Src kinase and key Src substrates that promote cell migration. Endogenous Src physically associated with keratin proteins in keratinocytes in a K6-dependent fashion. Purified Src bound K6-containing filaments via its SH2 domain in a novel phosphorylation-independent manner, resulting in kinase inhibition. K6 protein was enriched in the detergent-resistant membrane (DRM), a key site of Src inhibition, and DRMs from K6-null keratinocytes were depleted of both keratin and Src. We conclude that K6 negatively regulates Src kinase activity and the migratory potential of skin keratinocytes during wound repair. Our findings may also be important in related contexts such as cancer.

Original languageEnglish (US)
Pages (from-to)381-389
Number of pages9
JournalJournal of Cell Biology
Volume197
Issue number3
DOIs
StatePublished - Apr 2012

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Keratins
Keratinocytes
Keratin-6
Wounds and Injuries
src-Family Kinases
Type II Keratin
src Homology Domains
Epidermis
Detergents
Cell Movement
Phosphotransferases
Phosphorylation
Skin
Membranes
Genes
Neoplasms
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Medicine(all)

Cite this

A wound-induced keratin inhibits Src activity during keratinocyte migration and tissue repair. / Rotty, Jeremy D.; Coulombe, Pierre A.

In: Journal of Cell Biology, Vol. 197, No. 3, 04.2012, p. 381-389.

Research output: Contribution to journalArticle

Rotty, Jeremy D. ; Coulombe, Pierre A. / A wound-induced keratin inhibits Src activity during keratinocyte migration and tissue repair. In: Journal of Cell Biology. 2012 ; Vol. 197, No. 3. pp. 381-389.
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