Fig. 9. Schematic representation of TRAF-dependent PI 3-kinase pathways. The data presented in this paper are consistent with a pathway involving both Ras and Src as key molecules in generating TRAF6 and PI 3-kinase-dependent activation of actin-mediated changes in cell morphology. The schematic incorporates relevant pathways derived from other reports as described in the text. Solid black arrows connect sequential pathway elements, red arrows designate enzymatic action, and broken arrows indicate protein-protein interactions resulting in a directional activation, as indicated by arrowheads. The activation of NF-
B by TRAF6 is indicated by tandem arrows, representative of the multistep process involving I
B kinase-activated phosphorylation and degradation of I
B resulting in subsequent release of active p50
p65. Abbreviations: IL1RI
IL1RAcP, IL-1 ligand-binding transmembrane receptor complex comprising the type I and accessory receptors; TIR, Toll-IL-1/18 homology domain; DD, death domain; TIM, TRAF-interaction motif; WASP, Wiskott-Aldrich syndrome protein; PI, phosphatidylinositol; PIP, phosphatidylinositol 4-monophosphate; PIP2, phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2]; PIP3, phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P3]; PIP5Kinase, phosphatidylinositol-4-phosphate 5-kinase.