BANK1 and BLK act through phospholipase C gamma 2 in B-cell signaling

The B cell adaptor protein with ankyrin repeats (BANK1) and the B lymphoid tyrosine kinase (BLK) have been genetically associated with autoimmunity. The proteins of these genes interact physically and work in concert during B-cell signaling. Little is know about their interactions with other B-cell...

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Bibliographic Details
Published in:PloS one 2013-03, Vol.8 (3), p.e59842-e59842
Main Authors: Bernal-Quirós, Manuel, Wu, Ying-Yu, Alarcón-Riquelme, Marta E, Castillejo-López, Casimiro
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - metabolism
Ankyrins
Antigens
Arthritis
Autoimmunity
B-cell receptor
B-Lymphocytes - cytology
Biology
Cloning
Cloning, Molecular
Cluster Analysis
Fatty acids
Gene expression
Gene Expression Regulation, Enzymologic
Genes
Green Fluorescent Proteins - metabolism
HEK293 Cells
Humans
Immunoglobulin M - chemistry
Immunology
Immunoprecipitation
Kinases
Localization
Lupus
Lymphocytes B
Medical research
Medicine
Membrane Proteins - metabolism
Membranes
Molecular machines
Mutation
Phosphatase
Phospholipase
Phospholipase C
Phospholipase C gamma - metabolism
Phosphorylation
Proline
Protein Binding
Protein Structure, Tertiary
Protein-tyrosine kinase
Proteins
Signal Transduction
Signaling
src-Family Kinases - metabolism
Two-Hybrid System Techniques
Tyrosine
Yeast
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Summary:The B cell adaptor protein with ankyrin repeats (BANK1) and the B lymphoid tyrosine kinase (BLK) have been genetically associated with autoimmunity. The proteins of these genes interact physically and work in concert during B-cell signaling. Little is know about their interactions with other B-cell signaling molecules or their role in the process. Using yeast two hybrid (Y2H) we sought for factors that interact with BANK1. We found that the molecular switch PLCg2 interacts with BANK1 and that the interaction is promoted by B-cell receptor (BCR) stimulation. We found further that the kinase activity of BLK enhanced BANK1- PLCg2 binding and that the interaction was suppressed upon BLK depletion. Immunoprecipitation and mutational analysis demonstrated that the interaction between BANK1 and PLCg2 was dependent on specific tyrosine and proline residues on the adaptor protein. Our results provide new information important to understand the role of these two genes in basic B-cell physiology and immune-related diseases.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0059842