Regulation of phospholipase C-gamma2 and phosphoinositide 3-kinase pathways by adaptor proteins in B lymphocytes.
The importance of phosphoinositide 3-kinase (PI3K) and phospholipase C (PLC)-gamma2 in B cell function and development has been highlighted by gene targeting experiments in mice. In fact, these knockout mice exhibit a profound inhibition of proliferative responses upon B cell receptor (BCR) engagement. The molecular connections between these effectors and upstream tyrosine kinases such as Syk have been studied intensively in the past few years. This mechanism involves the action of cytoplasmic adaptor molecules, which participate in forming multicomponent signaling complexes, thereby directing the appropriate subcellular localization of effector enzymes. In addition to these cytoplasmic adaptor proteins, cell surface coreceptors can be viewed as transmembrane adaptor proteins, because coreceptors can also change the localization of effector enzymes, which in turn modulates the BCR-initiated signals.
Kurosaki
T
T
Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi, Japan. kurosaki@mxr.mesh.ne.jp
Okada
T
T
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D004792:Enzyme Precursors / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D051966:Phospholipase C gamma; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015398:Signal Transduction; D000072377:Syk Kinase; D010738:Type C Phospholipases / Q000378:metabolism*
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D010716:Phosphatidylinositols; D011947:Receptors, Antigen, B-Cell; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D010738:Type C Phospholipases; D051966:Phospholipase C gamma