act(p(HGNC:GSK3B)) directlyIncreases p(HGNC:MAPT, pmod(Ph, Ser, 202))

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PubMed:21734277

Filamentous, but not soluble, forms of wild-type tau inhibit anterograde, kinesin-based fast axonal transport (FAT) by activating axonal protein phosphatase 1 (PP1) and glycogen synthase kinase 3 (GSK3), independent of microtubule binding. Amino acids 2-18 of tau, comprising a phosphatase-activating domain (PAD), are necessary and sufficient for activation of this pathway. Various pathogenic forms of tau displaying increased exposure of PAD inhibited anterograde FAT in squid axoplasm. Immunohistochemical studies using a novel PAD-specific monoclonal antibody in human postmortem tissue indicated that increased PAD exposure represents an early pathogenic event in AD that closely associates in time with AT8 immunoreactivity. We propose a model of pathogenesis in which disease-associated changes in tau conformation lead to increased exposure of PAD, activation of PP1-GSK3, and inhibition of FAT

Related Edges 8

• bp(GO:"axonal transport") negativeCorrelation act(p(HGNC:PPP1CA))
• p(HBP:"phosphatase-activating domain") directlyIncreases act(p(HGNC:PPP1CA))
• act(p(HGNC:GSK3B)) directlyIncreases p(HGNC:MAPT, pmod(Ph, Ser, 199))
• act(p(HGNC:GSK3B)) directlyIncreases p(HGNC:MAPT, pmod(Ph, Thr, 205))
• p(HGNC:GSK3B, pmod(Ph, Ser, 9)) directlyDecreases act(p(HGNC:GSK3B))
• act(p(HGNC:PPP1CA)) directlyDecreases p(HGNC:GSK3B, pmod(Ph, Ser, 9))
• act(p(HGNC:PPP1CA)) increases act(p(HGNC:GSK3B))
• act(p(HGNC:PPP1CA)) negativeCorrelation bp(GO:"axonal transport")

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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.

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