PMID:12062087

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
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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	part_of:(GO:0071320)	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	exists_during:(GO:0071320)	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	has_input:(UniProtKB:Q55CL6) part_of:(GO:0019954)	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	part_of:(GO:0071320)	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	exists_during:(GO:0071320)	Seeded From UniProt	complete
DICDI:MP2K1	enables	GO:0004708: MAP kinase kinase activity	ECO:0000315: mutant phenotype evidence used in manual assertion		F	part_of:(GO:0043327)	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	exists_during:(GO:0071320)	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	has_input:(UniProtKB:Q55CL6) part_of:(GO:0071320)	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	exists_during:(GO:0071320)	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	part_of:(GO:0071320)	Seeded From UniProt	complete
DICDI:Q8N0B4	part_of	GO:0005938: cell cortex	ECO:0000314: direct assay evidence used in manual assertion		C	exists_during:(GO:0071320)	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

References

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