ACTIN CYTOSKELETON POLYMERIZATION IN DBL-TRANSFORMED NIH3T3 FIBROBLASTS IS DEPENDENT ON CELL-ADHESION TO SPECIFIC EXTRACELLULAR-MATRIX PROTEINS

The Dbl oncogene is the putative exchange factor for two small GTP-bin ding proteins, RhoA and CDC42 which are involved in the polymerization of actin to produce stress fibers and filopodia, respectively. We rep ort here that Dbl oncogene-transformed NIH3T3 cells show actin stress fibers only when cells are plated on fibronectin, Plating of cells on collagen I and IV as well as on poly-D-lysine and gelatin induces poly merization of actin to form filopodia, lamellipodia and membrane ruffl es but not stress fibers, The putative collagen receptors, alpha 1/bet a 1 and alpha 2/beta 1 integrins are expressed at reduced level in Dbl -transformed cells compared to untransformed NIH3T3 fibroblasts, Never theless, adhesion to collagens is not altered, Inhibitory monoclonal a ntibody to mouse integrin beta 1 subunit blocked adhesion of both Dbl- transformed and untransformed NIH3T3 cells, demonstrating that adhesio n to collagen I and TV is mediated by the beta 1 family of integrins. Dbl product rapidly induces the depolymerization of actin stress fiber s, rounding up of the cells, and formation of filopodia and lamellipod ia when microinjected in NIH3T3 cells plated on gelatin, Thus, Dbl may exert its effect on actin cytoskeleton organization in response to ex tracellular proteins by altering integrin-mediated signalling pathways .