Immunity 2003,
PMID: 14563325
Han, Arnold; Saijo, Kaoru; Mecklenbräuker, Ingrid; Tarakhovsky, Alexander; Nussenzweig, Michel C
Bam32 is an adaptor protein recruited to the plasma membrane upon B cell receptor (BCR) crosslinking in a phosphoinositol 3-kinase (PI3K)-dependent manner; however, its physiologic function is unclear. To determine its physiologic function, we produced Bam32-deficient mice. Bam32(-/-) B cells develop normally but have impaired T-independent antibody responses in vivo and diminished responses to BCR crosslinking in vitro. Biochemical analysis revealed that Bam32 acts in a novel pathway leading from the BCR to MAPK/ERK Kinases (MEK1/2), MAPK/ERK Kinase Kinase-1 (MEKK1), extracellular signal-regulated kinase (ERK), and c-jun NH2-terminal kinase (JNK), but not p38 mitogen-activated protein kinase (p38). This pathway appears to be initiated by hematopoietic progenitor kinase-1 (HPK1), which interacts directly with Bam32, and differs from all previously characterized BCR signaling pathways in that it is required for normal BCR-mediated proliferation but not for B cell survival.
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Text Mining Data
Dashed line = No text mining data
Manually curated Databases
-
IRef Hprd Interaction:
MAP4K1
—
DAPP1
(in vivo)
-
IRef Hprd Interaction:
MAP4K1
—
DAPP1
(in vitro)
-
NCI Pathway Database BCR signaling pathway:
Bam32/HPK1 complex (DAPP1-MAP4K1)
→
Bam32 (DAPP1)
(modification, collaborate)
Evidence: assay, physical interaction
-
NCI Pathway Database BCR signaling pathway:
Bam32/HPK1 complex (DAPP1-MAP4K1)
→
HPK1 (MAP4K1)
(modification, collaborate)
Evidence: assay, physical interaction
-
NCI Pathway Database BCR signaling pathway:
Bam32 (DAPP1)
→
HPK1 (MAP4K1)
(modification, collaborate)
Evidence: assay, physical interaction
-
NCI Pathway Database BCR signaling pathway:
RAC1 (RAC1)
→
TAK1 (MAP3K7)
(modification, activates)
Evidence: assay, physical interaction, other species
-
NCI Pathway Database BCR signaling pathway:
RAC1 (RAC1)
→
Bam32/HPK1 complex (DAPP1-MAP4K1)
(modification, activates)
Evidence: assay, physical interaction, other species
-
NCI Pathway Database BCR signaling pathway:
RAC1 (RAC1)
→
MEKK1 (MAP3K1)
(modification, activates)
Evidence: assay, physical interaction, other species
-
NCI Pathway Database BCR signaling pathway:
TAK1 (MAP3K7)
→
Bam32/HPK1 complex (DAPP1-MAP4K1)
(modification, activates)
Evidence: assay, physical interaction, other species
-
NCI Pathway Database BCR signaling pathway:
TAK1 (MAP3K7)
→
MEKK1 (MAP3K1)
(modification, activates)
Evidence: assay, physical interaction, other species
-
NCI Pathway Database BCR signaling pathway:
Bam32/HPK1 complex (DAPP1-MAP4K1)
→
MEKK1 (MAP3K1)
(modification, activates)
Evidence: assay, physical interaction, other species
In total, 12 gene pairs are associated to this article in curated databases