The polarity-inducing kinase Par-1 controls Xenopus gastrulation in cooperation with 14-3-3 and aPKC

EMBO J. 2004 Oct 27;23(21):4190-201. doi: 10.1038/sj.emboj.7600381. Epub 2004 Sep 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / metabolism*
  • Activins / metabolism
  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans Proteins
  • Cell Line
  • Cell Lineage
  • Gastrula / physiology*
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Molecular Sequence Data
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / metabolism
  • Protein Kinase C / metabolism*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proteins / metabolism
  • Sequence Alignment
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism*
  • Xenopus laevis

Substances

  • 14-3-3 Proteins
  • Caenorhabditis elegans Proteins
  • Isoenzymes
  • Oligonucleotides, Antisense
  • PARD6B protein, Xenopus
  • Proteins
  • Xenopus Proteins
  • par-6 protein, C elegans
  • Activins
  • MARK3 protein, Xenopus
  • Protein-Serine-Threonine Kinases
  • PKC-3 protein
  • Protein Kinase C