Figure 3.

Migration of MAC requires spatially controlled activation of RhoA. At the migration front various GAP (e.g., Myo9B, p120RasGAP) and other factors (e.g., BACURD2) that inhibit RhoA activity. Endopeptidases concentrated in podosomes mediate dissociation of the ECM which is necessary for MAC migration. Podosome formation is inhibited by RhoA. At the rear end RhoA activity is required for uropod retraction. RhoA is activated, e.g., by TNF-α via PI3K/PKC-.ζ signaling resulting in activation of ERM which, in turn, translocate RhoA to the membrane. TGF-β first promotes RhoA activity via an autocrine MIP-1α stimulation loop, but at later time points inhibits RhoA via PKA signaling and p190RhoGAP.