Abstract 2344 Mechanisms controlling synergistic activation of the autoinhibited Rac1 GEF complex, DOCK/ELMO

Guanine nucleotide exchange factors (GEFs) play an essential role in regulating small GTPase activity in numerous cell signaling pathways. The Dedicator of cytokinesis (DOCK)/Engulfment and cell motility (ELMO) protein complex is a Rac1 specific GEF that facilitates phosphatidylinositol-3-kinase beta (PI3KB) activation. Cells lacking functional DOCK/ELMO complexes exhibit defects in cell polarity and migration, which has been attributed to a reduction in cellular levels of PI(3,4,5)P3 lipids. Understanding the mechanisms that control the membrane recruitment and activation of DOCK/ELMO complexes is necessary to decipher how communication and feedback between small GTPases and phosphatidylinositol phosphate (PIP) lipids is regulated in cell signaling.