Bam32 links the B cell receptor to ERK and JNK and mediates B cell proliferation but not survival.
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.
Han
Arnold
A
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10021, USA.
Saijo
Kaoru
K
Mecklenbräuker
Ingrid
I
Tarakhovsky
Alexander
A
Nussenzweig
Michel C
MC
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology*; D048031:JNK Mitogen-Activated Protein Kinases; D008074:Lipoproteins; D008565:Membrane Proteins / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C403524:Dapp1 protein, mouse; D008074:Lipoproteins; D008565:Membrane Proteins; D011947:Receptors, Antigen, B-Cell; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases