Roles of PLC-β2 and -β3 and PI3Kγ in Chemoattractant-Mediated Signal Transduction

Abstract

The roles of phosphoinositide 3-kinase (PI3K) and phospholipase C (PLC) in chemoattractant-elicited responses were studied in mice lacking these key enzymes. PI3Kγ was required for chemoattractant-induced production of phosphatidylinositol 3,4,5-trisphosphate [PtdIns (3,4,5)P 3 ] and has an important role in chemoattractant-induced superoxide production and chemotaxis in mouse neutrophils and in production of T cell–independent antigen-specific antibodies composed of the immunoglobulin λ light chain (TI-Igλ L ). The study of the mice lacking PLC-β2 and -β3 revealed that the PLC pathways have an important role in chemoattractant-mediated production of superoxide and regulation of protein kinases, but not chemotaxis. The PLC pathways also appear to inhibit the chemotactic activity induced by certain chemoattractants and to suppress TI-Igλ L production.

Vaccinia virus impairs directional migration and chemokine receptor switch of human dendritic cells

“…Even more drastic was the failure of VV-infected DC to mobilize intracellular free calcium after triggering of CCR7. With regard to the interpretation of these results, it has been shown by several groups that the PI3Kc and PKB are essentially required for chemokine-induced migration of mouse leukocytes [35,36,46]. In contrast, the role of the MAPK pathways for chemotaxis is less clear, although its activation via chemokine receptors is well documented [33,[47][48][49].…”

“…Chemokine receptors belong to the family of G protein-coupled heptahelical-transmembrane receptors and transmit the signals for the process of directional migration by activation of the phosphoinositol-3-kinase c (PI3Kc) and the mitogen-activated protein kinase (MAPK) pathways [33][34][35][36][37][38]. We therefore assessed phosphorylation of extracellular signal-regulated kinase-1 and 2 (ERK1/2) and phosphorylation of protein kinase B (PKB), a major target of the PI3Kc, by Western blot after infection of DC with VV.…”

“…3A-C). Stimulation of chemokine receptors is also followed by mobilization of intracellular free calcium [33,36,39]. Thus, we assessed the capability of VV-infected DC to increase intracellular calcium levels after stimulation of chemokine receptors.…”

Lipid signalling in disease

“…PI3K , the only class IB PI3K isoform, is activated by subunits of trimeric G proteins that are dissociated by GPCRs to produce transient, but massive, elevations of PtdIns(3,4,5)P 3 . This lipid kinase integrates multiple signals from chemokines, complement fragments, formylated bacterial peptides and other stimuli, and was shown to be essential for chemokine-induced leukocyte migration in vivo [96][97][98] . Therefore, PI3K has become the subject of impressive pharmacological efforts as a target to treat inflammatory disease 5,99 .…”

BLT2 phosphorylation at Thr355by Akt is necessary for BLT2-mediated chemotaxis

“…Akt plays critical roles in various cellular responses, including chemotactic migration [15][16][17]. Also, BLT2 mediates chemotaxis after stimulation with its ligand LTB 4 [3,16].…”