Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
Par (partitioning-defective) genes were originally identified in Caenorhabditis elegans as determinants of anterior/posterior polarity. However, neither their function in vertebrate development nor their action mechanism has been fully addressed. Here we show that two members of Par proteins, 14-3-3 (Par-5) and atypical PKC (aPKC), regulate the serine/threonine kinase Par-1 to control Xenopus gastrulation. We find first that Xenopus Par-1 (xPar-1) is essential for gastrulation but not for cell fate specification during early embryonic development. We then find that xPar-1 binds to 14-3-3 in an aPKC-dependent manner. Our analyses identify two aPKC phosphorylation sites in xPar-1, which are essential for 14-3-3 binding and for proper gastrulation movements. The aPKC phosphorylation-dependent binding of xPar-1 to 14-3-3 does not markedly affect the kinase activity of xPar-1, but induces relocation of xPar-1 from the plasma membranes to the cytoplasm. Finally, we show that Xenopus aPKC and its binding partner Xenopus Par-6 are also essential for gastrulation. Thus, our results identify a requirement of Par proteins for Xenopus gastrulation and reveal a novel interrelationship within Par proteins that may provide a general mechanism for spatial control of Par-1.
Amaya,
Expression of a dominant negative mutant of the FGF receptor disrupts mesoderm formation in Xenopus embryos.
1991, Pubmed,
Xenbase
Amaya,
Expression of a dominant negative mutant of the FGF receptor disrupts mesoderm formation in Xenopus embryos.
1991,
Pubmed
,
Xenbase Benton,
Drosophila 14-3-3/PAR-5 is an essential mediator of PAR-1 function in axis formation.
2002,
Pubmed Benton,
Drosophila PAR-1 and 14-3-3 inhibit Bazooka/PAR-3 to establish complementary cortical domains in polarized cells.
2003,
Pubmed Bessone,
EMK protein kinase-null mice: dwarfism and hypofertility associated with alterations in the somatotrope and prolactin pathways.
1999,
Pubmed Brajenovic,
Comprehensive proteomic analysis of human Par protein complexes reveals an interconnected protein network.
2004,
Pubmed Chang,
14-3-3 epsilon positively regulates Ras-mediated signaling in Drosophila.
1997,
Pubmed Deardorff,
Frizzled-8 is expressed in the Spemann organizer and plays a role in early morphogenesis.
1998,
Pubmed
,
Xenbase Djiane,
Role of frizzled 7 in the regulation of convergent extension movements during gastrulation in Xenopus laevis.
2000,
Pubmed
,
Xenbase Drewes,
MARK, a novel family of protein kinases that phosphorylate microtubule-associated proteins and trigger microtubule disruption.
1997,
Pubmed Du,
Identification of distinct classes and functional domains of Wnts through expression of wild-type and chimeric proteins in Xenopus embryos.
1995,
Pubmed
,
Xenbase Etemad-Moghadam,
Asymmetrically distributed PAR-3 protein contributes to cell polarity and spindle alignment in early C. elegans embryos.
1995,
Pubmed Etienne-Manneville,
Cell polarity: Par6, aPKC and cytoskeletal crosstalk.
2003,
Pubmed Guo,
par-1, a gene required for establishing polarity in C. elegans embryos, encodes a putative Ser/Thr kinase that is asymmetrically distributed.
1995,
Pubmed Habas,
Coactivation of Rac and Rho by Wnt/Frizzled signaling is required for vertebrate gastrulation.
2003,
Pubmed
,
Xenbase Heasman,
Beta-catenin signaling activity dissected in the early Xenopus embryo: a novel antisense approach.
2000,
Pubmed
,
Xenbase Hung,
PAR-6 is a conserved PDZ domain-containing protein that colocalizes with PAR-3 in Caenorhabditis elegans embryos.
1999,
Pubmed Hurov,
Atypical PKC phosphorylates PAR-1 kinases to regulate localization and activity.
2004,
Pubmed Hurov,
Immune system dysfunction and autoimmune disease in mice lacking Emk (Par-1) protein kinase.
2001,
Pubmed Joberty,
The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42.
2000,
Pubmed Keller,
The patterning and functioning of protrusive activity during convergence and extension of the Xenopus organiser.
1992,
Pubmed
,
Xenbase Kemphues,
Identification of genes required for cytoplasmic localization in early C. elegans embryos.
1988,
Pubmed Kinoshita,
PKC delta is essential for Dishevelled function in a noncanonical Wnt pathway that regulates Xenopus convergent extension movements.
2003,
Pubmed
,
Xenbase Kusakabe,
Xenopus FRS2 is involved in early embryogenesis in cooperation with the Src family kinase Laloo.
2001,
Pubmed
,
Xenbase Macara,
Parsing the polarity code.
2004,
Pubmed Moon,
Xwnt-5A: a maternal Wnt that affects morphogenetic movements after overexpression in embryos of Xenopus laevis.
1993,
Pubmed
,
Xenbase Morton,
The Caenorhabditis elegans par-5 gene encodes a 14-3-3 protein required for cellular asymmetry in the early embryo.
2002,
Pubmed Müller,
C-TAK1 regulates Ras signaling by phosphorylating the MAPK scaffold, KSR1.
2001,
Pubmed Nakaya,
Meiotic maturation induces animal-vegetal asymmetric distribution of aPKC and ASIP/PAR-3 in Xenopus oocytes.
2000,
Pubmed
,
Xenbase Ohno,
Intercellular junctions and cellular polarity: the PAR-aPKC complex, a conserved core cassette playing fundamental roles in cell polarity.
2001,
Pubmed Ossipova,
Molecular cloning and developmental expression of Par-1/MARK homologues XPar-1A and XPar-1B from Xenopus laevis.
2002,
Pubmed Peng,
C-TAK1 protein kinase phosphorylates human Cdc25C on serine 216 and promotes 14-3-3 protein binding.
1998,
Pubmed Shi,
Hippocampal neuronal polarity specified by spatially localized mPar3/mPar6 and PI 3-kinase activity.
2003,
Pubmed Sokol,
Analysis of Dishevelled signalling pathways during Xenopus development.
1996,
Pubmed
,
Xenbase Sun,
PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signalling.
2001,
Pubmed
,
Xenbase Tabuse,
Atypical protein kinase C cooperates with PAR-3 to establish embryonic polarity in Caenorhabditis elegans.
1998,
Pubmed Tada,
Xwnt11 is a target of Xenopus Brachyury: regulation of gastrulation movements via Dishevelled, but not through the canonical Wnt pathway.
2000,
Pubmed
,
Xenbase Tzivion,
14-3-3 proteins: active cofactors in cellular regulation by serine/threonine phosphorylation.
2002,
Pubmed Uberall,
Conventional PKC-alpha, novel PKC-epsilon and PKC-theta, but not atypical PKC-lambda are MARCKS kinases in intact NIH 3T3 fibroblasts.
1997,
Pubmed Wallingford,
Convergent extension: the molecular control of polarized cell movement during embryonic development.
2002,
Pubmed
,
Xenbase Winklbauer,
Frizzled-7 signalling controls tissue separation during Xenopus gastrulation.
2001,
Pubmed
,
Xenbase
