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.
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
Ursula
U
Rescher
Carsten
C
Ludwig
Vera
V
Konietzko
Alexei
A
Kharitonenkov
Volker
V
Gerke
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