Tyrosine phosphorylation of annexin A2 regulates Rho-mediated actin rearrangement and cell adhesion.
Cell adhesion and motility require a dynamic remodelling of the membrane-associated actin cytoskeleton in response to extracellular stimuli that are primarily transmitted through receptor tyrosine kinases. In a cellular model system for tyrosine phosphorylation-based growth factor signaling, we observed that annexin A2 is tyrosine-phosphorylated upon insulin receptor activation. The phosphorylation precedes peripheral actin accumulations and subsequent cell detachment. These morphological changes are inhibited by annexin A2 depletion and require Rho/ROCK signaling downstream of tyrosine-phosphorylated annexin A2. A phospho-mimicking annexin A2 mutant is sufficient to drive peripheral actin accumulation and the resulting cell detachment in the absence of insulin stimulation. Thus, a tyrosine phosphorylation switch in annexin A2 is an important event in triggering Rho/ROCK-dependent and actin-mediated changes in cell morphology associated with the control of cell adhesion.
Rescher
Ursula
U
Institute of Medical Biochemistry, Centre for Molecular Biology of Inflammation, and Interdisciplinary Clinical Research Centre, University of Muenster, 48149 Muenster, Germany. rescher@uni-muenster.de
Ludwig
Carsten
C
Konietzko
Vera
V
Kharitonenkov
Alexei
A
Gerke
Volker
V
D000199:Actins / Q000378:metabolism*; D017306:Annexin A2 / Q000378:metabolism*; D002448:Cell Adhesion; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism
D000199:Actins; D017306:Annexin A2; D014443:Tyrosine; D054460:rho-Associated Kinases