A. Epithelial cells expressing control vector or constitutively
active forms of the ABL kinases were grown in collagen gels and stained for the
apical polarity marker gp135, the adherens junction marker E-cadherin and the
nuclear DAPI stain. Active ABL2, and to a lesser extent ABL1, promote polarity
inversion. All pictures were taken at 40× magnification. Scale bar: 25
μm. B. Model for the inversion of epithelial cell polarity
by active ABL kinase. Activation of ABL downstream of RTKs, chemokine receptors,
oxidative stress and other signals leads to disruption of β1-integrin
signaling and localization by regulation of the Rap1 GTPase via ABL2-mediated
phosphorylation of CRK and disruption of the CRK-C3G (RAPGEF1) complex. Active
ABL2 also impairs Rac1-mediated laminin assembly in epithelial cysts111.