Four-jointed Is a Golgi Kinase That Phosphorylates a Subset of Cadherin Domains

Ishikawa, Hiroyasu; Takeuchi, Hideyuki; Haltiwanger, Robert S.; Irvine, Kenneth D.

doi:10.1126/science.1158159

Cited by 241 publications

(241 citation statements)

References 30 publications

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“…4B), suggesting that Gb'Lft promotes mitosis to activate expression of cyclin E, probably mediated by Hpo/Sav/Wts pathway, in the both regenerating leg and contralateralnormal leg. The Ds/Ft signaling molecule Four-jointed (Fj), which encodes a Golgi kinase to phosphorylate the extracellular domains of Ds and Ft and to regulate the interaction between them (Ishikawa et al, 2008;Brittle et al, 2010;Simon et al, 2010), is involved in cell proliferation, because Gb'fj RNAi nymphs exhibit a slightly shorter regenerating leg (Bando et al, 2009). Yki and Arm encode a downstream transcriptional co-activator of the Hpo/Sav/Wts pathway and a downstream transcription factor of Wg/Wnt signaling, respectively.…”

Section: Discussionmentioning

confidence: 99%

Lowfat, a mammalian Lix1 homologue, regulates leg size and growth under the Dachsous/Fat signaling pathway during tissue regeneration†

Bando

Hamada

Kurita

et al. 2011

Developmental Dynamics

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In the cricket Gryllus bimaculatus, missing distal parts of amputated legs are regenerated from blastemas based on positional information. The Dachsous/Fat (Ds/Ft) signaling pathway regulates blastema cell proliferation and positional information along the longitudinal axis during leg regeneration. Herein, we show that the Gryllus homologue of Lowfat (Gb'Lft), which modulates Ds/Ft signaling in Drosophila, is involved in leg regeneration. Gb'lft is expressed in regenerating legs, and RNAi against Gb'lft (Gb'lft RNAi ) suppressed blastema cell hyperproliferation caused by Gb'ft RNAi or Gb'ds RNAi but enhanced that caused by Gb'kibra RNAi or Gb'warts RNAi . In Gb'lft RNAi nymphs, missing parts of amputated legs were regenerated, but the length of the regenerated legs was shortened depending on the position of the amputation. Both normal and reversed intercalary regeneration occurred in Gb'lft RNAi nymphs, suggesting that Gb'Lft is involved in blastema cell proliferation and longitudinal leg regeneration under the Ds/Ft signaling pathway, but it is not required for intercalary regeneration.

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Section: Discussionmentioning

confidence: 99%

Lowfat, a mammalian Lix1 homologue, regulates leg size and growth under the Dachsous/Fat signaling pathway during tissue regeneration†

Bando

Hamada

Kurita

et al. 2011

Developmental Dynamics

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“…Because Ft-95 is too C-terminal to include the cadherin domains (Fig. S1), the phosphorylation detected presumably reflects a phosphorylation of the intracellular domain, rather than Fj-mediated phosphorylation of cadherin domains (2). To investigate the relationship between Ft-95 phosphorylation and Fat signaling, Fat was examined in lysates of wing imaginal discs in which its putative ligand, ds, was either mutant or overexpressed.…”

Section: Resultsmentioning

confidence: 99%

“…However, molecular mechanisms associated with activation of Fat by Ds have not been described. The influence of Ds on Fat appears to be modulated by Four-jointed, a Golgi kinase that phosphorylates cadherin domains of Fat and Ds (2).…”

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confidence: 99%

Processing and phosphorylation of the Fat receptor

Feng

Irvine

2009

Proc. Natl. Acad. Sci. U.S.A.

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140

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The Drosophila tumor suppressors fat and discs overgrown (dco) function within an intercellular signaling pathway that controls growth and polarity. fat encodes a transmembrane receptor, but post-translational regulation of Fat has not been described. We show here that Fat is subject to a constitutive proteolytic processing, such that most or all cell surface Fat comprises a heterodimer of stably associated N-and C-terminal fragments. The cytoplasmic domain of Fat is phosphorylated, and this phosphorylation is promoted by the Fat ligand Dachsous. dco encodes a kinase that influences Fat signaling, and Dco is able to promote the phosphorylation of the Fat intracellular domain in cultured cells and in vivo.

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“…Ds is also a large (>3,000 amino acids) atypical cadherin with 27 cadherin domains (Clark et al, 1995). The efficiency of their heterodimer formation is modulated by a Golgi-localized protein kinase Fourjointed (Fj) (Villano and Katz, 1995;Matakatsu and Blair, 2004;Ishikawa et al, 2008), which phosphorylates Ft and Ds (Brittle et al, 2010;Simon et al, 2010). Ds-Ft are thought to be a ligand-receptor pair that acts via the atypical myosin Dachs (D) (Mao et al, 2006), whose localization in a cell reflects the Ft activity (Matakatsu and Blair, 2008;Rogulja et al, 2008).…”

Section: Fig 2 Drosophila Adult Leg Phenotypes Ofmentioning

confidence: 99%

Regulation of leg size and shape: Involvement of the Dachsous‐fat signaling pathway

Bando

Mito

Nakamura

et al. 2011

Developmental Dynamics

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How limb size and shape is regulated is a long-standing question in developmental and regeneration biology. Recently, the protocadherin Dachsous-Fat (Ds-Ft) signaling pathway has been found to be essential for wing development of the fly and leg regeneration of the cricket. The Ds-Ft signaling pathway is linked to the Warts-Hippo (Wts-Hpo) signaling pathway, leading to cell proliferation. Several lines of evidence have suggested that the Wts-Hpo signaling pathway is involved in the control of organ size, and that this pathway is regulated by Ds-Ft and Merlin-Expanded, which are linked to morphogens such as decapentaplegic/bone morphogenic protein, Wingless/Wnt, and epidermal growth factor. Here we review recent progress in elucidating mechanisms controlling leg size and shape in insects and vertebrates, focusing on the Ds-Ft signaling pathway. We also introduce a working model, Ds-Ft steepness model, to explain how steepness of the Ds-Ft gradient controls leg size along the proximodistal axis. Developmental Dynamics 240:1028-1041,

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Four-jointed Is a Golgi Kinase That Phosphorylates a Subset of Cadherin Domains

Abstract: The atypical cadherin Fat acts as a receptor for a signaling pathway that regulates growth, gene expression, and planar cell polarity

Cited by 241 publications

References 30 publications

Lowfat, a mammalian Lix1 homologue, regulates leg size and growth under the Dachsous/Fat signaling pathway during tissue regeneration†

Lowfat, a mammalian Lix1 homologue, regulates leg size and growth under the Dachsous/Fat signaling pathway during tissue regeneration†

Processing and phosphorylation of the Fat receptor

Regulation of leg size and shape: Involvement of the Dachsous‐fat signaling pathway

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