title: Essential role of integrin-linked kinase in regulation of phagocytosis in keratinocytes.
abstract: 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.
authors: Department of Physiology and Pharmacology, Medical Sciences Bldg., University of Western Ontario, London, ON Canada, N6A 5C1.
authors: Samar
authors: S
authors: Sayedyahossein
authors: Lylia
authors: L
authors: Nini
authors: Timothy S
authors: TS
authors: Irvine
authors: Lina
authors: L
authors: Dagnino
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D015151:Immunoblotting; D015603:Keratinocytes / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D010587:Phagocytosis / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000235:genetics / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D000099200:Scaffold Protein ILK
chemical_list: D017346:Protein Serine-Threonine Kinases; D044464:Receptor, PAR-2; D020830:rac1 GTP-Binding Protein; D000099200:Scaffold Protein ILK