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Essential role of integrin‐linked kinase in regulation of phagocytosis in keratinocytes
Author(s) -
Sayedyahossein Samar,
Nini Lylia,
Irvine Timothy S.,
Dagnino Lina
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.12-207852
Subject(s) - microbiology and biotechnology , integrin linked kinase , pseudopodia , phagocytosis , rac1 , signal transduction , biology , chemistry , kinase , protein kinase a , actin , cyclin dependent kinase 2
Phagocytic melanosome uptake by epidermal keratinocytes is a central protective mechanism against damage induced by ultraviolet radiation. Phagocytosis requires formation of pseudopodia via actin cytoskeleton rearrangements. Integrin‐linked kinase (ILK) is an important modulator of actin cytoskeletal dynamics. We have examined the role of ILK in regulation of phagocytosis, using epidermal keratinocytes isolated from mice with epidermis‐restricted Ilk gene inactivation. ILK‐deficient cells exhibited severely impaired capacity to engulf fluorescent microspheres in response to stimulation of the keratinocyte growth factor (KGF) receptor or the protease‐activated receptor‐2. KGF induced ERK phosphorylation in ILK‐expressing and ILK‐deficient cells, suggesting that ILK is not essential for KGF receptor signaling. In contrast, KGF promoted activation of Rac1 and formation of pseudopodia in ILK‐expressing, but not in ILK‐deficient cells. Rac1‐deficient keratinocytes also showed substantially impaired phagocytic ability, underlining the importance of ILK‐dependent Rac1 function for particle engulfment. Finally, cross‐modulation of KGF receptors by integrins may be another important element, as integrin β1‐deficient keratinocytes also fail to show significant phagocytosis in response to KGF. Thus, we have identified a novel signaling pathway essential for phagocytosis in keratinocytes, which involves ILK‐dependent activation of Rac1 in response to KGF, resulting in the formation of pseudopodia and particle uptake.—Sayedyahossein, S., Nini, L., Irvine, T. S., and Dagnino, L., Essential role of integrin‐linked kinase in regulation of phagocytosis in keratinocytes. FASEB J. 26, 4218–4229 (2012). www.fasebj.org