MAP kinase and Wnt pathways converge to downregulate an HMG-domain repressor in Caenorhabditis elegans

Nature. 1999 Jun 24;399(6738):793-7. doi: 10.1038/21666.

Abstract

The signalling protein Wnt regulates transcription factors containing high-mobility-group (HMG) domains to direct decisions on cell fate during animal development. In Caenorhabditis elegans, the HMG-domain-containing repressor POP-1 distinguishes the fates of anterior daughter cells from their posterior sisters throughout development, and Wnt signalling downregulates POP-1 activity in one posterior daughter cell called E. Here we show that the genes mom-4 and lit-1 are also required to downregulate POP-1, not only in E but also in other posterior daughter cells. Consistent with action in a common pathway, mom-4 and lit-1 exhibit similar mutant phenotypes and encode components of the mitogen-activated protein kinase (MAPK) pathway that are homologous to vertebrate transforming-growth-factor-beta-activated kinase (TAK1) and NEMO-like kinase (NLK), respectively. Furthermore, MOM-4 and TAK1 bind related proteins that promote their kinase activities. We conclude that a MAPK-related pathway cooperates with Wnt signal transduction to downregulate POP-1 activity. These functions are likely to be conserved in vertebrates, as TAK1 and NLK can downregulate HMG-domain-containing proteins related to POP-1.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / enzymology
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins*
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Line
  • Cloning, Molecular
  • DNA-Binding Proteins / genetics*
  • Down-Regulation*
  • Enzyme Activation
  • Gene Expression Regulation, Developmental
  • Genes, Helminth
  • High Mobility Group Proteins / genetics*
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • JNK Mitogen-Activated Protein Kinases*
  • MAP Kinase Kinase 4
  • MAP Kinase Kinase Kinases*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mitogen-Activated Protein Kinase Kinases*
  • Mitogen-Activated Protein Kinases*
  • Molecular Sequence Data
  • Potassium Channels, Voltage-Gated
  • Protein Kinases / metabolism
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism*
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Wnt Proteins
  • Zebrafish Proteins*

Substances

  • Adaptor Proteins, Signal Transducing
  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • Intracellular Signaling Peptides and Proteins
  • KCNQ1OT1 long non-coding RNA, human
  • Membrane Proteins
  • Potassium Channels, Voltage-Gated
  • Proto-Oncogene Proteins
  • TAB1 protein, MAPKKK activator, vertebrate
  • TAB1 protein, human
  • Wnt Proteins
  • Zebrafish Proteins
  • mom-4 protein, C elegans
  • pop-1 protein, C elegans
  • Protein Kinases
  • NLK protein, human
  • Protein-Serine-Threonine Kinases
  • lit-1 protein, C elegans
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinases
  • MAP kinase kinase kinase 7
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases

Associated data

  • GENBANK/AF145375
  • GENBANK/AF145376
  • GENBANK/AF145377