Model for Par1b regulation of IRSp53 in epithelial lumen formation. Activated Rac1 or Cdc42 recruit Rho-GTPase effector proteins such as Mena, WAVE, mDia, and Eps8 involved in microfilament organization to the IRSp53 SH3 domain. Phosphorylation of S366 by Par1b and Par1b stimulation of S434-5 phosphorylation by an unidentified kinase recruits 14-3-3 proteins that interfere with WAVE2 binding and the recruitment of other proteins that interact with the IRSp53 C-terminal domain. Par1b overexpression inhibits IRSp53-dependent actin dynamics that regulate cell–ECM signaling and result in altered lumen polarity in MDCK cells. In other cell types, such as Cos7, unidentified kinases inhibit IRSp53 function by creating 14-3-3 binding sites on T340/T360.