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PMID:10391246

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Citation

Meneghini, MD, Ishitani, T, Carter, JC, Hisamoto, N, Ninomiya-Tsuji, J, Thorpe, CJ, Hamill, DR, Matsumoto, K and Bowerman, B (1999) MAP kinase and Wnt pathways converge to downregulate an HMG-domain repressor in Caenorhabditis elegans. Nature 399:793-7

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.

Links

PubMed Online version:10.1038/21666

Keywords

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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CAEEL:TAB1

involved_in

GO:0001714: endodermal cell fate specification

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00006524

P

Seeded From UniProt

complete

CAEEL:TAB1

enables

GO:0030295: protein kinase activator activity

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(UniProtKB:Q9XTC6)

Seeded From UniProt

complete

CAEEL:TAB1

enables

GO:0031435: mitogen-activated protein kinase kinase kinase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9XTC6

F

Seeded From UniProt

complete

CAEEL:TAB1

involved_in

GO:0045860: positive regulation of protein kinase activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:MOM2

involved_in

GO:0045167: asymmetric protein localization involved in cell fate determination

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00094666

P

Seeded From UniProt

complete

CAEEL:PORCN

involved_in

GO:0045167: asymmetric protein localization involved in cell fate determination

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00094648

P

Seeded From UniProt

complete

CAEEL:NLK

involved_in

GO:0001714: endodermal cell fate specification

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00094680

P

Seeded From UniProt

complete

CAEEL:NLK

involved_in

GO:0008356: asymmetric cell division

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00094680

P

Seeded From UniProt

complete

CAEEL:NLK

involved_in

GO:0045167: asymmetric protein localization involved in cell fate determination

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00094680

P

Seeded From UniProt

complete

CAEEL:NLK

involved_in

GO:0042694: muscle cell fate specification

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00249122

P

Seeded From UniProt

complete

CAEEL:MOM4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:G5EEM6

F

Seeded From UniProt

complete

CAEEL:MOM4

involved_in

GO:0001714: endodermal cell fate specification

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00094649
WB:WBVar00094665

P

Seeded From UniProt

complete

CAEEL:MOM4

involved_in

GO:0000165: MAPK cascade

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:MOM4

involved_in

GO:0008356: asymmetric cell division

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00094665

P

Seeded From UniProt

complete

CAEEL:MOM4

enables

GO:0004709: MAP kinase kinase kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:MOM4

involved_in

GO:0006468: protein phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:MOM4

involved_in

GO:0045167: asymmetric protein localization involved in cell fate determination

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00094665

P

Seeded From UniProt

complete

CAEEL:MOM4

involved_in

GO:0042694: muscle cell fate specification

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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