B-cell linker (BLNK)

Functions as a central linker protein, downstream of the B-cell receptor (BCR), bridging the SYK kinase to a multitude of signaling pathways and regulating biological outcomes of B-cell function and development. Plays a role in the activation of ERK/EPHB2, MAP kinase p38 and JNK. Modulates AP1 activation. Important for the activation of NF-kappa-B and NFAT. Plays an important role in BCR-mediated PLCG1 and PLCG2 activation and Ca2+ mobilization and is required for trafficking of the BCR to late endosomes. However, does not seem to be required for pre-BCR-mediated activation of MAP kinase and phosphatidyl-inositol 3 (PI3) kinase signaling. May be required for the RAC1-JNK pathway. Plays a critical role in orchestrating the pro-B cell to pre-B cell transition. May play an important role in BCR-induced B-cell apoptosis.

B-cell linker (BLNK) Related Areas

Immunology>>Adaptive Immunity>>B Cell>>BLNK/Ly-57/SLP-65

Signal Transduction>>Adaptor Protein>>BLNK/Ly-57/SLP-65

B-cell linker (BLNK) Alternative Names

BLNK, Ly-57, SLP-65, BASH, BLNK-S, LY57, MGC111051, SLP65 [Homo sapiens]

Blnk, Ly-57, SLP-65, BASH, Bca, Ly57, Lyw-57 [Mus musculus]

Summaries for B-cell linker (BLNK)

Entrez Gene summary for B-cell linker (BLNK):

This gene encodes a cytoplasmic linker or adaptor protein that plays a critical role in B cell development. This protein bridges B cell receptor-associated kinase activation with downstream signaling pathways, thereby affecting various biological functions. The phosphorylation of five tyrosine residues is necessary for this protein to nucleate distinct signaling effectors following B cell receptor activation. Mutations in this gene cause hypoglobulinemia and absent B cells, a disease in which the pro- to pre-B-cell transition is developmentally blocked. Deficiency in this protein has also been shown in some cases of pre-B acute lymphoblastic leukemia. Alternatively spliced transcript variants have been found for this gene

OMIM - description for B-cell linker (BLNK):

The BLNK gene encodes a B-cell linker protein. Linker or adaptor proteins provide mechanisms by which receptors can amplify and regulate downstream effector proteins. BLNK is essential for normal B-cell development

Wikipedia summary for B-cell linker (BLNK):

The B-cell linker protein is encoded by the BLNK gene and is an adaptor protein also known as SLP-65,BASH,and BCA. BLNK is expressed in B cells and macrophages and plays a large role in B cell receptor signalling, in a fashion analogous to the role its paralogue SLP-76 plays in T cell receptor signalling.As it has no known intrinsic enzymatic activity, the function of BLNK is to temporally and spatially coordinate and regulate signalling effectors downstream of the B cell receptor.

Human B-cell linker (BLNK) Protein General Information

 

• Protein names: Recommended name: B-cell linker protein
• Sequence length: 456 AA.
• Domain: SH2 domain
• Sequence similarities: Contains 1 SH2 domain.
• Post-translational modification: Following BCR activation, phosphorylated on tyrosine residues by SYK and LYN. When phosphorylated, serves as a scaffold to assemble downstream targets of antigen activation, including PLCG1, VAV1, GRB2 and NCK1. Phosphorylation of Tyr-84, Tyr-178 and Tyr-189 facilitates PLCG1 binding. Phosphorylation of Tyr-96 facilitates BTK binding. Phosphorylation of Tyr-72 facilitates VAV1 and NCK1 binding. Phosphorylation is required for both Ca2+ and MAPK signaling pathways.
• Subunit structure: Associates with PLCG1, VAV1 and NCK1 in a B-cell antigen receptor-dependent fashion. Interacts with VAV3, PLCG2 and GRB2. Interacts through its SH2 domain with CD79A. Interacts (via SH2 domain) with SYK; phosphorylated and activated by SYK. Interacts with SCIMP
• Subcellular location: Cytoplasm. Cell membrane. Note: BCR activation results in the translocation to membrane fraction.
• Tissue specificity: Expressed in B-cell lineage and fibroblast cell lines (at protein level). Highest levels of expression in the spleen, with lower levels in the liver, kidney, pancreas, small intestines and colon.
• Involvement in disease: Defects in BLNK are the cause of agammaglobulinemia type 4 (AGM4) [MIM:613502]. It is a primary immunodeficiency characterized by profoundly low or absent serum antibodies and low or absent circulating B-cells due to an early block of B-cell development. Affected individuals develop severe infections in the first years of life

General information above from UniProt

Function for B-cell linker (BLNK) Protein

UniProtKB:

Functions as a central linker protein, downstream of the B-cell receptor (BCR), bridging the SYK kinase to a multitude of signaling pathways and regulating biological outcomes of B-cell function and development. Plays a role in the activation of ERK/EPHB2, MAP kinase p38 and JNK. Modulates AP1 activation. Important for the activation of NF-kappa-B and NFAT. Plays an important role in BCR-mediated PLCG1 and PLCG2 activation and Ca2+ mobilization and is required for trafficking of the BCR to late endosomes. However, does not seem to be required for pre-BCR-mediated activation of MAP kinase and phosphatidyl-inositol 3 (PI3) kinase signaling. May be required for the RAC1-JNK pathway. Plays a critical role in orchestrating the pro-B cell to pre-B cell transition. May play an important role in BCR-induced B-cell apoptosis.

Genatlas:

• B-cell linker (BLNK) is adaptor molecule crucial for normal B-cell development
• B-cell linker (BLNK) is involved in T cell antigen receptor mediated signaling
• B-cell linker (BLNK) is a important adaptor protein selectively expressed in B-lineage cells
• B-cell linker (BLNK) recruits active H-Ras to the B cell receptor (BCR) complex, which is essential for sustained surface expression of BCR in the form of the cap and for the signal leading to functional ERK activation

Homology for human B-cell linker (BLNK)

• ortholog to murine Blnk

Phenotype Information for B-cell linker (BLNK)

• Gene/Locus: BLNK, SLP65, AGM4
• Phenotype: Agammaglobulinemia 4

Phenotype Information for B-cell linker (BLNK) from OMIM (Online Mendelian Inheritance in Man)