Abstract
Signaling through the B cell receptor (BCR) is essential for B cell function and development. Despite the key role of Syk in BCR signaling, little is known about the mechanism by which Syk transmits downstream effectors. BLNK (B cell LiNKer protein), a substrate for Syk, is now shown to be essential in activating phospholipase C (PLC)gamma 2 and JNK. The BCR-induced PLC gamma 2 activation, but not the JNK activation, was restored by introduction of PLC gamma 2 membrane-associated form into BLNK-deficient B cells. As JNK activation requires both Rac1 and PLC gamma 2, our results suggest that BLNK regulates the Rac1-JNK pathway, in addition to modulating PLC gamma 2 localization.
MeSH Terms
Adaptor Proteins, Signal Transducing
Amino Acid Sequence
Animals
B-Lymphocytes/enzymology,metabolism
Calcium Signaling
Calcium-Calmodulin-Dependent Protein Kinases/metabolism
Carrier Proteins/genetics,metabolism,physiology
Cell Membrane/enzymology
Chickens
Enzyme Activation
Enzyme Precursors/metabolism
GTP-Binding Proteins/metabolism
Humans
Intracellular Signaling Peptides and Proteins
Isoenzymes/biosynthesis,genetics,metabolism
JNK Mitogen-Activated Protein Kinases
Mice
Mitogen-Activated Protein Kinases
Molecular Sequence Data
Phospholipase C gamma
Phosphoproteins
Phosphorylation
Protein-Tyrosine Kinases/metabolism
Receptors, Antigen, B-Cell/metabolism,physiology
Recombinant Fusion Proteins/biosynthesis
Syk Kinase
Type C Phospholipases/biosynthesis,genetics,metabolism
Tyrosine/metabolism
rac GTP-Binding Proteins
ras Proteins/metabolism
Chemicals
Adaptor Proteins, Signal Transducing
B cell linker protein
Carrier Proteins
Enzyme Precursors
Intracellular Signaling Peptides and Proteins
Isoenzymes
Phosphoproteins
Receptors, Antigen, B-Cell
Recombinant Fusion Proteins
Tyrosine
Protein-Tyrosine Kinases
SYK protein, human
Syk Kinase
Syk protein, mouse
Calcium-Calmodulin-Dependent Protein Kinases
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases
Type C Phospholipases
Phospholipase C gamma
GTP-Binding Proteins
rac GTP-Binding Proteins
ras Proteins
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Ishiai M
Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi, Japan.
Kurosaki M
Pappu R
Okawa K
Ronko I
Fu C
Shibata M
Iwamatsu A
Chan A C
Kurosaki T