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PMID:12062087

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Citation

Sobko, A, Ma, H and Firtel, RA (2002) Regulated SUMOylation and ubiquitination of DdMEK1 is required for proper chemotaxis. Dev. Cell 2:745-56

Abstract

MEK1, which is required for aggregation and chemotaxis in Dictyostelium, is rapidly and transiently SUMOylated in response to chemoattractant stimulation. SUMOylation is required for MEK1's function and its translocation from the nucleus to the cytosol and cortex, including the leading edge of chemotaxing cells. MEK1 in which the site of SUMOylation is mutated is retained in the nucleus and does not complement the mek1 null phenotype. Constitutively active MEK1 is cytosolic and is constitutively SUMOylated, whereas the corresponding nonactivatable MEK1 is not SUMOylated and nuclear. MEK1 is also ubiquitinated in response to signaling. A MEK1-interacting, ubiquitin E3 ligase RING domain-containing protein controls nuclear localization and MEK1 ubiquitination. These studies provide a pathway regulating the localization and function of MEK1.

Links

PubMed

Keywords

Amino Acid Sequence; Animals; Cell Aggregation; Cell Nucleus/metabolism; Chemotaxis/physiology; Cysteine/metabolism; Cytosol/metabolism; Dictyostelium; Humans; Ligases/metabolism; Mitogen-Activated Protein Kinase Kinases/metabolism; Models, Biological; Molecular Sequence Data; Mutation; Protein Structure, Tertiary; Protein Transport; Protozoan Proteins; Recombinant Fusion Proteins/metabolism; Sequence Homology, Amino Acid; Signal Transduction; Small Ubiquitin-Related Modifier Proteins/metabolism; Ubiquitin-Protein Ligases

Significance

Annotations

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

DICDI:ERK1

enables

GO:0004707: MAP kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DICDI:ERK1

is_active_in

GO:0031252: cell leading edge

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DICDI:ERK1

is_active_in

GO:0005938: cell cortex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DICDI:Q557I6

acts_upstream_of_or_within

GO:0030010: establishment of cell polarity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DICDI:Q557I6

involved_in

GO:0016567: protein ubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DICDI:Q557I6

is_active_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DICDI:Q557I6

acts_upstream_of_or_within

GO:0031152: aggregation involved in sorocarp development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DICDI:Q557I6

enables

GO:0031434: mitogen-activated protein kinase kinase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q55CL6

F

Seeded From UniProt

complete

DICDI:Q557I6

involved_in

GO:0051457: maintenance of protein location in nucleus

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DICDI:Q557I6

acts_upstream_of_or_within

GO:0043327: chemotaxis to cAMP

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DICDI:Q557I6

enables

GO:0061630: ubiquitin protein ligase activity

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(UniProtKB:Q55CL6)

Seeded From UniProt

complete

DICDI:MP2K1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8N0B4

F

Seeded From UniProt

complete

DICDI:MP2K1

involved_in

GO:0000187: activation of MAPK activity

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(UniProtKB:P42525)

Seeded From UniProt

complete

DICDI:MP2K1

involved_in

GO:0000165: MAPK cascade

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DICDI:MP2K1

part_of

GO:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DICDI:MP2K1

enables

GO:0004708: MAP kinase kinase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

DICDI:MP2K1

is_active_in

GO:0031252: cell leading edge

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DICDI:MP2K1

is_active_in

GO:0005938: cell cortex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DICDI:MP2K1

involved_in

GO:0072697: protein localization to cell cortex

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(UniProtKB:P42525)
  • happens_during:(GO:0071320)

Seeded From UniProt

complete

DICDI:Q8N0B4

involved_in

GO:0016925: protein sumoylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DICDI:Q8N0B4

enables

GO:0019789: SUMO transferase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DICDI:Q8N0B4

is_active_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DICDI:Q8N0B4

part_of

GO:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DICDI:Q8N0B4

enables

GO:0031434: mitogen-activated protein kinase kinase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q55CL6

F

Seeded From UniProt

complete

DICDI:Q8N0B4

part_of

GO:0005938: cell cortex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DICDI:Q8N0B4

involved_in

GO:1904778: positive regulation of protein localization to cell cortex

ECO:0000314: direct assay evidence used in manual assertion

P

  • happens_during:(GO:0071320)
  • has_input:(UniProtKB:Q55CL6)

Seeded From UniProt

complete

DICDI:MP2K1

part_of

GO:0031252: cell leading edge

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DICDI:MP2K1

colocalizes_with

GO:0005938: cell cortex

ECO:0000314: direct assay evidence used in manual assertion

C

exists_during:(GO:0071320)

Seeded From UniProt

complete

DICDI:MP2K1

colocalizes_with

GO:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

exists_during:(GO:0071320)

Seeded From UniProt

complete

DICDI:MP2K1

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DICDI:MP2K1

enables

GO:0004708: MAP kinase kinase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

happens_during:(GO:0071320)

Seeded From UniProt

complete

DICDI:MP2K1

acts_upstream_of_or_within

GO:0000165: MAPK cascade

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DICDI:MP2K1

acts_upstream_of_or_within

GO:0043327: chemotaxis to cAMP

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DICDI:MP2K1

involved_in

GO:0000187: activation of MAPK activity

ECO:0000314: direct assay evidence used in manual assertion

P

regulates_activity_of:(UniProtKB:P42525)

Seeded From UniProt

complete

DICDI:MP2K1

enables

GO:0043130: ubiquitin binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q557I6

F

Seeded From UniProt

complete

DICDI:ERK1

acts_upstream_of_or_within

GO:0043327: chemotaxis to cAMP

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DICDI:ERK1

colocalizes_with

GO:0031252: cell leading edge

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DICDI:ERK1

acts_upstream_of_or_within

GO:0031152: aggregation involved in sorocarp development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DICDI:ERK1

involved_in

GO:0006468: protein phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DICDI:ERK1

colocalizes_with

GO:0005938: cell cortex

ECO:0000314: direct assay evidence used in manual assertion

C

exists_during:(GO:0071320)

Seeded From UniProt

complete

DICDI:ERK1

part_of

GO:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DICDI:ERK1

enables

GO:0004707: MAP kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

activated_by:(CHEBI:17489)

Seeded From UniProt

complete

DICDI:ERK1

acts_upstream_of_or_within

GO:0000165: MAPK cascade

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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