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