Rho-Kinase Phosphorylates PAR-3 and Disrupts PAR Complex Formation

Nakayama, Masanori; Goto, Takaaki; Sugimoto, Masayuki; Nishimura, Takashi; Shinagawa, Takafumi; Ohno, Shigeo; Amano, Mutsuki; Kaibuchi, Kozo

doi:10.1016/j.devcel.2007.11.021

Cited by 136 publications

(153 citation statements)

References 40 publications

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“…Unlike Par6, Par3-Ser 962 phosphorylation does not appear to be involved in aPKC activation because the inhibition of aPKC (15) and suppression of Aurora A result in different phenotypes. Par3 phosphorylation at Ser 962 could change the affinity for its interaction partners, as it has been reported for other kinases such as aPKC, ROK, and Src family kinases (33)(34)(35). Phosphorylation of Par3 at Tyr 1127 reduces the association of Par3 with LIM kinase 2 (35,36).…”

Section: Discussionmentioning

confidence: 95%

Phosphorylation of the Par Polarity Complex Protein Par3 at Serine 962 Is Mediated by Aurora A and Regulates Its Function in Neuronal Polarity

Khazaei¹,

Püschel

2009

Journal of Biological Chemistry

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The Aurora kinases are a family of serine/threonine protein kinases that perform important functions during the cell cycle. Recently, it was shown that Drosophila Aurora A also regulates the asymmetric localization of Numb to the basal and the partitioning-defective (Par) complex to the apical cortex of neuroblasts by phosphorylating Par6. Here, we show that Aurora A is required for neuronal polarity. Suppression of Aurora A by RNA interference results in the loss of neuronal polarity. Aurora A interacts directly with the atypical protein kinase C binding domain of Par3 and phosphorylates it at serine 962. The phosphorylation of Par3 at serine 962 contributes to its function in the establishment of neuronal polarity.

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Section: Discussionmentioning

confidence: 95%

Phosphorylation of the Par Polarity Complex Protein Par3 at Serine 962 Is Mediated by Aurora A and Regulates Its Function in Neuronal Polarity

Khazaei¹,

Püschel

2009

Journal of Biological Chemistry

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“…The constructs of pcDNA3.1-, pCAG-and pEGFP-Daple fragments, and pEGFP-PKCλ were produced as described elsewhere 34,48 . Enhanced green fluorescent protein was fused to the NT, and V5 and myc tags were fused to the CT of the proteins.…”

Section: Plasmidsmentioning

confidence: 99%

The Dishevelled-associating protein Daple controls the non-canonical Wnt/Rac pathway and cell motility

et al. 2012

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Dishevelled is the common mediator of canonical and non-canonical Wnt signalling pathways, which are important for embryonic development, tissue maintenance and cancer progression. In the non-canonical Wnt signalling pathway, the Rho family of small GTPases acting downstream of Dishevelled has essential roles in cell migration. The mechanisms by which the non-canonical Wnt signalling pathway regulates Rac activation remain unknown. Here we show that Daple (Dishevelled-associating protein with a high frequency of leucine residues) regulates Wnt5a-mediated activation of Rac and formation of lamellipodia through interaction with Dishevelled. Daple increases the association of Dishevelled with an isoform of atypical protein kinase C, consequently promoting Rac activation. Accordingly, Daple deficiency impairs migration of fibroblasts and epithelial cells during wound healing in vivo. These findings indicate that Daple interacts with Dishevelled to direct the Dishevelled/protein kinase λ protein complex to activate Rac, which in turn mediates the non-canonical Wnt signalling pathway required for cell migration.

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“…PAR polarity proteins are essential for appropriate control of cytoskeletal, and thus cellular, polarity in a wide variety of polarized cell types (Mertens et al 2005;Nishimura et al 2005;Macara 2006, 2008;Pegtel et al 2007;Nakayama et al 2008;St Johnston and Ahringer 2010). Baz/Par interaction with the Rac-GEF, TIAM, regulates actin dynamics in a number of different systems (Nishimura et al 2005;Zhang and Macara 2006;Heasman and Ridley 2008), and contributes to TJ formation in epithelia (Chen and Macara 2005;Mertens et al 2005;Gopalakrishnan et al 2007).…”

Section: Branched Actin Networkmentioning

confidence: 99%

“…3). ROCK phosphorylation of PAR-3 disrupted PAR-3/ aPKC/PAR-6 complex formation in migrating cells, spatially controlling TIAM-mediated Rac activity (Nakayama et al 2008). Zallen and colleagues reported a mechanism whereby ROCK regulates the Baz/PAR-3 PI interaction, thus controlling Baz/PAR-3 association with the cortex (Simoes Sde et al 2010).…”

Section: Contractile Actomyosin Networkmentioning

confidence: 99%

Phosphoinositides in Cell Architecture

Shewan

Eastburn²,

Mostov

2011

Cold Spring Harbor Perspectives in Biology

173

159

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Inositol phospholipids have been implicated in almost all aspects of cellular physiology including spatiotemporal regulation of cellular signaling, acquisition of cellular polarity, specification of membrane identity, cytoskeletal dynamics, and regulation of cellular adhesion, motility, and cytokinesis. In this review, we examine the critical role phosphoinositides play in these processes to execute the establishment and maintenance of cellular architecture. Epithelial tissues perform essential barrier and transport functions in almost all major organs. Key to their development and function is the establishment of epithelial cell polarity. We place a special emphasis on highlighting recent studies demonstrating phosphoinositide regulation of epithelial cell polarity and how individual cells use phosphoinositides to further organize into epithelial tissues.P hosphoinositides (PIs) are essential components of cellular membranes in eukaryotes. Though these specialized lipids comprise less than 1% of the cellular lipid cohort, they play key roles in many fundamental biological processes (Di Paolo and De Camilli 2006;Saarikangas et al. 2010). PIs possess such far ranging roles by serving as specialized membrane docking sites for effectors of numerous cellular signal transduction cascades. PIs also serve as precursors of lipid second messengers. They are concentrated on the cytosolic face of cellular membranes (Fig. 1A) and rapidly diffuse within the plane of the membrane. Reversible phosphorylation of the myo-inositol head group of phosphatidylinositol (PtdIns) at positions 3, 4, and 5 (Fig. 1B) gives rise to the seven PI isoforms identified in eukaryotic cells. PtdIns(4)P and PtdIns(4,5)P 2 are constitutively present in membranes and comprise the largest pool of cellular PIs, whereas PtdIns(3,4,5)P 3 is essentially undetectable in most types of unstimulated cells (Lemmon and Ferguson 2000;Saarikangas et al. 2010).The spatiotemporally regulated production and turnover of phosphoinositides is crucial for localized PI signaling and function. Numerous phosphatidylinositol kinases and phosphatases are involved in regulating the metabolism of the various PI isoforms (Fig. 1)

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Rho-Kinase Phosphorylates PAR-3 and Disrupts PAR Complex Formation

Cited by 136 publications

References 40 publications

Phosphorylation of the Par Polarity Complex Protein Par3 at Serine 962 Is Mediated by Aurora A and Regulates Its Function in Neuronal Polarity

Phosphorylation of the Par Polarity Complex Protein Par3 at Serine 962 Is Mediated by Aurora A and Regulates Its Function in Neuronal Polarity

The Dishevelled-associating protein Daple controls the non-canonical Wnt/Rac pathway and cell motility

Phosphoinositides in Cell Architecture

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