Ephrin-A5 modulates cell adhesion and morphology in an integrin-dependent manner.
The ephrins are membrane-tethered ligands for the Eph receptor tyrosine kinases, which play important roles in patterning of the nervous and vascular systems. It is now clear that ephrins are more than just ligands and can also act as signalling-competent receptors, participating in bidirectional signalling. We have recently shown that ephrin-A5 signals within caveola-like domains of the plasma membrane upon engagement with its cognate Eph receptor, leading to increased adhesion of the cells to fibronectin. Here we show that ephrin-A5 controls sequential biological events that are consistent with its role in neuronal guidance. Activation of ephrin-A5 induces an initial change in cell adhesion followed by changes in cell morphology. Both effects are dependent on the activation of beta1 integrin involving members of the Src family of protein tyrosine kinases. The prolonged activation of ERK-1 and ERK-2 is required for the change in cell morphology. Our work suggests a new role for class A ephrins in specifying the affinity of the cells towards various extracellular substrates by regulating integrin function.
Davy
A
A
Departments of Oncology and Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada.
Robbins
S M
SM
D016475:3T3 Cells; D000818:Animals; D002448:Cell Adhesion; D048429:Cell Size; D002478:Cells, Cultured; D004789:Enzyme Activation; D036386:Ephrin-A5; D005353:Fibronectins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D017261:Glycosylphosphatidylinositols; D019012:Integrin beta1 / Q000737:chemistry / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016501:Neurites / Q000378:metabolism; D009842:Oligopeptides; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D036082:Receptor, EphA1; D012160:Retina / Q000166:cytology / Q000196:embryology; D014162:Transfection; D019061:src-Family Kinases / Q000378:metabolism
D036386:Ephrin-A5; D005353:Fibronectins; D017261:Glycosylphosphatidylinositols; D019012:Integrin beta1; D008565:Membrane Proteins; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D036082:Receptor, EphA1; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse; D019061:src-Family Kinases; D020928:Mitogen-Activated Protein Kinases