细胞信号通路ppt细胞信号通路大全上下细胞信号通路ppt gsk3_signaling.pptVIP

APC GBP GSK3 Signaling Frizzled Frizzled Growth FactorReceptor Gα-Q/O LEF/TCF CBP Dsh Gα-Q/O GBP CSNK1/2 Dsh P CSNK1/2 PI3K MAPKAPK1 β-Ctnn GTP β-TRCP β-Ctnn Akt/PKB PP2A β-Ctnn eIF2B eIF2 β-Ctnn b-CtnnDegradation WNT On-State Off-State β-Ctnn Cadherins GSK3 AXIN P P P P Ub Ub Ub CTBP Gene Expression Translation CSNK1/2 Ub Proteosome GrowthFactor MAPK APC TLE Ras 2009 ProteinL C * Review: GSK3 (Glycogen Synthase Kinase-3) is a ubiquitously expressed, highly conserved serine/threonine protein kinase found in all eukaryotes. Identified originally as a regulator of glycogen metabolism, GSK3 acts as a downstream regulatory switch for numerous signaling pathways, including cellular responses to WNT, Growth Factors, Insulin, RTK (Receptor Tyrosine Kinases), Hedgehog pathways, and GPCR (G-Protein-Coupled Receptors) and is involved in a wide range of signal transduction cascades involving cellular processes, ranging from glycogen metabolism, cell development, gene transcription, protein translation to cytoskeletal organization, cell cycle regulation, proliferation and apoptosis. Unlike most protein kinases involved in signaling, GSK3 is active in unstimulated, resting cells and its activity is diminished during cellular responses. Another peculiarity compared with other protein kinases is its preference for primed substrates, that is, substrates previously phosphorylated by another kinase (Ref.1). Growth Factors and Insulin signaling inhibit the ability of GSK3 to act on pre-phosphorylated (primed) substrates by phosphorylating Ser9 of GSK3, which then blocks the interaction of GSK3 with the phosphate group on primed substrates (Ref.2). GSK3 is localized predominantly in the cytoplasm but is also found in the nucleus. Its subcellular localization is changed in response to stimuli. There are two mammalian GSK3 isoforms encoded by distinct genes: GSK3-Alpha and GSK3-Beta. GSK3-Beta is particularly abundant in the CNS (Central Nervous System) and directly phosphor