Phosphorylation of Tau Is Regulated by PKN

Taniguchi, Tohru; Kawamata, Toshio; Mukai, Hideyuki; Hasegawa, Hiroshi; Isagawa, Takayuki; Yasuda, Minoru; Hashimoto, Takeshi; Terashima, Akira; Nakai, Masamichi; Mori, Hiroshi; Ono, Yoshitaka; Tanaka, Chikako

doi:10.1074/jbc.m007427200

Cited by 82 publications

(69 citation statements)

References 35 publications

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“…Rho activation of rhophilin-rhotekin-PKN signalling increases actin depolymerisation through ␣-actinin (Raftopoulou and Hall, 2004). In addition, PKN phosphorylates Tau, which destabilises microtubules (Taniguchi et al, 2001). Although citron-K regulates mouse cortical dendrite outgrowth (Di Cunto et al, 2003), we are not aware of any previous evidence for roles for PKN or citron-K in growth cone guidance.…”

Section: How Does Asymmetric Gtpase Activity Bias Growth Cone Advancementioning

confidence: 81%

Temporally and spatially coordinated roles for Rho, Rac, Cdc42 and their effectors in growth cone guidance by a physiological electric field

Rajnicek

Foubister

McCaig

2006

Journal of Cell Science

101

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Although it is known that neuronal growth cones migrate towards the cathode of an applied direct current (DC) electric field (EF), resembling the EF present in the developing nervous system, the underlying mechanism remains unclear. Here, we demonstrate temporally and spatially coordinated roles for the GTPases Rac, Cdc42 and Rho and their effectors. Growth cones of cultured Xenopus embryonic spinal neurons turned towards the cathode but collective inhibition of Rho, Rac and Cdc42 attenuated turning. Selective inhibition of Rho, Cdc42 or Rac signalling revealed temporally distinct roles in steering by an electrical gradient. Rho, Rac and Cdc42 are each essential for turning within the initial 2 hours (early phase). Later, Rho and Cdc42 signals remain important but Rac signalling dominates. The EF increased Rho immunofluorescence anodally. This correlated spatially with collapsed growth cone morphology and reduced anodal migration rates, which were restored by Rho inhibition. These data suggest that anodally increased Rho activity induces local cytoskeletal collapse, biasing growth cone advance cathodally. Collapse might be mediated by the Rho effectors p160 Rho kinase and myosin light chain kinase since their inhibition attenuated early turning. Inhibitors of phosphoinositide 3-kinase, MEK1/2 or p38 mitogen-activated protein kinase (MAPK) did not affect turning behaviour, eliminating them mechanistically. We propose a mechanism whereby Rac and Cdc42 activities dominate cathodally and Rho activity dominates anodally to steer growth cones towards the cathode. The interaction between Rho GTPases, the cytoskeleton and growth cone dynamics is explored in the companion paper published in this issue. Our results complement studies of growth cone guidance by diffusible chemical gradients and suggest that growth cones might interpret these co-existing guidance cues selectively.

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Section: How Does Asymmetric Gtpase Activity Bias Growth Cone Advancementioning

confidence: 81%

Temporally and spatially coordinated roles for Rho, Rac, Cdc42 and their effectors in growth cone guidance by a physiological electric field

Rajnicek

Foubister

McCaig

2006

Journal of Cell Science

101

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“…The complexity of the arisen interactions and the difficulty of comprehending their nature necessitate further in-depth studies on various low and high molecular mass phosphorylated substrates toward neurotoxic aluminum. Such studies encompass phosphorylated aminoacids and peptides [75], and are currently under investigation in our labs.…”

Section: Correlation Of the Aqueous Binary Al(iii)-phosphonate Speciamentioning

confidence: 99%

Synthetic, structural and solution speciation studies on binary Al(III)–(carboxy)phosphonate systems. Relevance to the neurotoxic potential of Al(III)

Georgantas

Kotsakis

Raptopoulou

et al. 2009

Journal of Inorganic Biochemistry

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“…In addition, several potential substrates for the kinase activity of PKN or PRK2 have been reported. These include phospholipase D, Graf/Graf2, neurofilaments, vimentin, tau, glial fibrillary acidic protein, and MLTKa (Mukai et al 1996b;Matsuzawa et al 1997;Oishi et al 2001;Shibata et al 2001;;Taniguchi et al 2001;Takahashi et al 2003). But again, the in vivo relevance of these phosphorylations is not clear.…”

Section: T He Rho Family Small Gtpases Play a Fundamentalmentioning

confidence: 99%

A Rho-Binding Protein Kinase C-Like Activity Is Required for the Function of Protein Kinase N in Drosophila Development

Betson

Settleman

2007

Genetics

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The Rho GTPases interact with multiple downstream effectors to exert their biological functions, which include important roles in tissue morphogenesis during the development of multicellular organisms. Among the Rho effectors are the protein kinase N (PKN) proteins, which are protein kinase C (PKC)-like kinases that bind activated Rho GTPases. The PKN proteins are well conserved evolutionarily, but their biological role in any organism is poorly understood. We previously determined that the single Drosophila ortholog of mammalian PKN proteins, Pkn, is a Rho/Rac-binding kinase essential for Drosophila development. By performing “rescue” studies with various Pkn mutant constructs, we have defined the domains of Pkn required for its role during Drosophila development. These studies suggested that Rho, but not Rac binding is important for Pkn function in development. In addition, we determined that the kinase domain of PKC53E, a PKC family kinase, can functionally substitute for the kinase domain of Pkn during development, thereby exemplifying the evolutionary strategy of “combining” functional domains to produce proteins with distinct biological activities. Interestingly, we also identified a requirement for Pkn in wing morphogenesis, thereby revealing the first postembryonic function for Pkn.

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Phosphorylation of Tau Is Regulated by PKN

Cited by 82 publications

References 35 publications

Temporally and spatially coordinated roles for Rho, Rac, Cdc42 and their effectors in growth cone guidance by a physiological electric field

Temporally and spatially coordinated roles for Rho, Rac, Cdc42 and their effectors in growth cone guidance by a physiological electric field

Synthetic, structural and solution speciation studies on binary Al(III)–(carboxy)phosphonate systems. Relevance to the neurotoxic potential of Al(III)

A Rho-Binding Protein Kinase C-Like Activity Is Required for the Function of Protein Kinase N in Drosophila Development

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