EphA1 interacts with integrin-linked kinase and regulates cell morphology and motility.
The Eph-ephrin receptor-ligand system is implicated in cell behavior and morphology. EphA1 is the founding member of the Eph receptors, but little is known about its function. Here, we show that activation of EphA1 kinase inhibits cell spreading and migration in a RhoA-ROCK-dependent manner. We also describe a novel interaction between EphA1 and integrin-linked kinase (ILK), a mediator of interactions between integrin and the actin cytoskeleton. The C-terminal sterile alpha motif (SAM) domain of EphA1 is required and the ankyrin region of ILK is sufficient for the interaction between EphA1 and ILK. The interaction is independent of EphA1 kinase activity but dependent on stimulation of the EphA1 ligand ephrin-A1. Activation of EphA1 kinase resulted in a decrease of ILK activity. Finally, we demonstrated that expression of a kinase-active form of ILK (S343D) rescued the EphA1-mediated spreading defect, and attenuated RhoA activation. These results suggest that EphA1 regulates cell morphology and motility through the ILK-RhoA-ROCK pathway.
Yamazaki
Tohru
T
Department of Pharmacology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
Masuda
Junko
J
Omori
Tsutomu
T
Usui
Ryosuke
R
Akiyama
Hitomi
H
Maru
Yoshiro
Y
D000577:Amides / Q000494:pharmacology; D017487:Ankyrins / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000201:enzymology; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics; D011725:Pyridines / Q000494:pharmacology; D036082:Receptor, EphA1 / Q000235:genetics / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000187:drug effects / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D000099200:Scaffold Protein ILK
D000577:Amides; D017487:Ankyrins; D004791:Enzyme Inhibitors; D017346:Protein Serine-Threonine Kinases; D011725:Pyridines; D036082:Receptor, EphA1; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; D000099200:Scaffold Protein ILK; C108830:Y 27632