B-cell linker protein (cytoplasmic adapter protein, B-cell adapter containing SH2 domain protein, B-cell adapter containing Src homology 2 domain protein, Src homology 2 domain-containing leukocyte protein of 65 kD, SLP-65, BLNK, BASH, SLP65)
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Function
- central linker protein that bridges the B-cell receptor- associated kinases with signaling pathways
- regulates biologic outcomes of B-cell function & development
- BCR-mediated PLCG1 activation & Ca+2 mobilization.
- RAC1-JNK pathway signaling
- orchestrates pro-B cell to pre-B cell transition
- antigen receptor-dependent association with PLCG1, VAV1, GRB2, NCK1
- following BCR activation, phosphorylated on TYR by SYK & LYN
- when phosphorylated, serves as scaffold to assemble downstream targets of antigen activation, including PLCG1, VAV1, GRB2, NCK1
- phosphorylation of Tyr-84, Tyr-178 & Tyr-189 facilitates PLCG1 binding
- phosphorylation of Tyr-96 facilitates BTK binding
- phosphorylation of Tyr-72 facilitates VAV1 & NCK1 binding
- phosphorylation is required for both Ca+2 & MAPK signaling pathways
- NOT required for pre-BCR-mediated activation of MAP kinase & PI3 kinase signaling
Compartment
- cytoplasm, membrane
- BCR activation results in the translocation to membrane
Alternative splicing
named isoforms=2
Expression
- expressed in B-cell lineage & fibroblast cell lines
- expression in spleen > liver, kidney, pancreas, small intestine, colon
Pathology
- defects in BLNK are the cause of hypoglobulinemia & absent B-cells
- diminished or absent BLNK expression in 6 of 34 childhood pre-B acute lymphoblastic leukemia