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PMID:16249387

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Citation

Ahn, E, Lee, H and Yun, Y (2006) LIME acts as a transmembrane adapter mediating BCR-dependent B-cell activation. Blood 107:1521-7

Abstract

Assembly of a signaling complex around the transmembrane adapter LAT is essential for the transmission of T-cell receptor (TCR)-mediated signaling. However, a LAT-like molecule responsible for the initial activation events in B-cell receptor (BCR) signaling has not yet been identified. Here, we show that LIME is a transmembrane adaptor required for BCR-mediated B-cell activation. LIME was found to be expressed in mouse splenic B cells. Upon BCR cross-linking, LIME was tyrosine phosphorylated by Lyn and associated with Lyn, Grb2, PLC-gamma2, and PI3K. Reduction of LIME expression by the introduction of siRNA resulted in the disruption of BCR-mediated activation of MAPK, calcium flux, NF-AT, PI3K, and NF-kappaB. Taken together, these results establish that LIME is an essential transmembrane adaptor linking BCR ligation to the downstream signaling events that lead to B-cell activation.

Links

PubMed Online version:10.1182/blood-2005-05-1859

Keywords

Adaptor Proteins, Vesicular Transport/immunology; Animals; B-Lymphocytes/immunology; Base Sequence; DNA Primers; Lymphocyte Activation; Mice; Plasmids; RNA, Small Interfering/genetics; Receptors, Antigen, T-Cell/immunology; Signal Transduction/immunology; Transfection

Significance

Annotations

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

MOUSE:LYN

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q9EQR5

F

Seeded From UniProt

complete

MOUSE:LYN

acts_upstream_of_or_within

GO:0018108: peptidyl-tyrosine phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:P85A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q9EQR5

F

Seeded From UniProt

complete

MOUSE:GRB2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q9EQR5

F

Seeded From UniProt

complete

MOUSE:PLCG2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q9EQR5

F

Seeded From UniProt

complete

MOUSE:LIME1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q8CIH5

F

Seeded From UniProt

complete

MOUSE:LIME1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q60631

F

Seeded From UniProt

complete

MOUSE:LIME1

enables

GO:0019901: protein kinase binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P25911
PR:P26450

F

Seeded From UniProt

complete

MOUSE:LIME1

part_of

GO:0019815: B cell receptor complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:LIME1

acts_upstream_of_or_within

GO:0014066: regulation of phosphatidylinositol 3-kinase signaling

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:LIME1

acts_upstream_of_or_within

GO:0006357: regulation of transcription by RNA polymerase II

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:LIME1

acts_upstream_of_or_within

GO:0051279: regulation of release of sequestered calcium ion into cytosol

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:LIME1

acts_upstream_of_or_within

GO:0043405: regulation of MAP kinase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:LIME1

acts_upstream_of_or_within

GO:0043122: regulation of I-kappaB kinase/NF-kappaB signaling

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:LIME1

acts_upstream_of_or_within

GO:0050853: B cell receptor signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:LIME1

acts_upstream_of_or_within

GO:1901222: regulation of NIK/NF-kappaB signaling

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TF65

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:TF65

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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