Members of the transforming growth factor-beta (TGFB) family signal through type I and type II serine/threonine-kinase receptors, which in turn activate the SMAD signaling pathway. Bone morphogenetic protein (BMP) receptors target SMAD1, SMAD5, and SMAD8, whereas receptors for activin and TGFB (e.g., ACVR1 and TGFBR1, respectively) target SMAD2 and SMAD3. Phosphorylation of these receptor-regulated SMADs induces their association with the common-partner SMAD, SMAD4. Smurf1, a HECT domain E3 ubiquitin ligase, regulates cell polarity and protrusive activity and is required to maintain the transformed morphology and motility of a tumor cell. Atypical protein kinase C-zeta (PKC2), an effector of the Cdc42/Rac1-PAR6 polarity complex, recruits Smurf1 to cellular protrusions, where it controlled the local level of RhoA. Smurf1 thus links the polarity complex to degradation of RhoA in lamellipodia and filopodia to prevent RhoA signaling during dynamic membrane movements.