The B-cell linker protein is encoded by the ''BLNK''

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and is an adaptor protein also known as SLP-65, BASH, and BCA. BLNK is expressed in

B cell B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...

s and

macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...

s and plays a large role in

B cell receptor The B cell receptor (BCR) is a transmembrane protein on the surface of a B cell. A B cell receptor is composed of a membrane-bound immunoglobulin molecule and a signal transduction moiety. The former forms a type 1 transmembrane receptor protein, ...

signalling, in a fashion analogous to the role its paralogue

SLP-76 Lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa), also known as LCP2 or SLP-76, is a signal-transducing adaptor protein expressed in T cells and myeloid cells and is important in the signaling of T-cell recepto ...

plays in

T cell receptor The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The binding b ...

signalling. As it has no known intrinsic enzymatic activity, the function of BLNK is to temporally and spatially coordinate and regulate signalling effectors

downstream Downstream may refer to: * Downstream (bioprocess) * Downstream (manufacturing) * Downstream (networking) * Downstream (software development) * Downstream (petroleum industry) * Upstream and downstream (DNA), determining relative positions on DNA ...

of the

Function

The function of BLNK was first illustrated in BLNK deficient DT40 cells, a

chicken The chicken (''Gallus gallus domesticus'') is a domesticated junglefowl species, with attributes of wild species such as the grey and the Ceylon junglefowl that are originally from Southeastern Asia. Rooster or cock is a term for an adult m ...

B-cell B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted o ...

line, which exhibited an abrogated intracellular calcium mobilisation response and impaired activation of MAP kinases p38,

JNK c-Jun N-terminal kinases (JNKs), were originally identified as kinases that bind and phosphorylate c-Jun on Ser-63 and Ser-73 within its transcriptional activation domain. They belong to the mitogen-activated protein kinase family, and ar ...

, and to a lesser degree ERK upon B-cell receptor (BCR) activation as compared to wild type DT40 cells. In

knockout mice A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...

, BLNK deficiency results in a partial block in B-cell development, and in humans BLNK deficiency results in a much more profound block in B-cell development. Linker or adaptor proteins provide mechanisms by which receptors can amplify and regulate downstream effector proteins. The B-cell linker protein is essential for normal B-cell development. upplied by OMIMref name="entrez"/>

Structure

BLNK consists of a N-terminal

leucine zipper A leucine zipper (or leucine scissors) is a common three-dimensional structural motif in proteins. They were first described by Landschulz and collaborators in 1988 when they found that an enhancer binding protein had a very characteristic 30-amin ...

motif followed by an "acidic" region, a proline-rich region, and a C-terminal

SH2 domain The SH2 (Src Homology 2) domain is a structurally conserved protein domain contained within the Src oncoprotein and in many other intracellular signal-transducing proteins. SH2 domains allow proteins containing those domains to dock to phosphory ...

. The leucine zipper motif allows BLNK to localise to the plasma membrane, presumably by coiled-coil interactions with a membrane protein. This leucine zipper motif distinguishes BLNK from its paralogue SLP-76 which, although having an N-terminal heptad-like organisation of leucine and isoleucine residues, has not been experimentally shown to have this motif. Recruitment of BLNK to the plasma membrane is also achieved by binding of the SH2 domain of BLNK to a non- ITAM phospho-tyrosine on Igα, a part of the B cell receptor complex. The acidic region of BLNK contains several inducibly phosphorylated tyrosine residues, at least five in humans, that mediate protein-protein interactions between BLNK and PLCγ2, Btk, Vav, and

Nck NCK (Newton Chambers Koehring), started as a subsidiary of Newton, Chambers & Company, a large engineering company based in Sheffield, England. They produced the range of agricultural equipment, skimmers, excavators, Crane (machine), cranes and ...

. A more recent mass spectrometry study of BLNK in DT40 cells found that at least 41 unique serine, threonine, and tyrosine residues are phosphorylated on BLNK.

Interactions

B-cell linker has been shown to

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with Grb2,

SH3KBP1 SH3 domain-containing kinase-binding protein 1 (synonyms - CIN85, in rodents - Ruk) is an adaptor protein that in humans is encoded by the ''SH3KBP1'' gene. Function CBL (MIM 165360) constitutively interacts with SH3 domain-containing protein ...

CD79A Cluster of differentiation CD79A also known as B-cell antigen receptor complex-associated protein alpha chain and MB-1 membrane glycoprotein, is a protein that in humans is encoded by the CD79A gene. The CD79a protein together with the related CD ...

MAP4K1 Mitogen-activated protein kinase kinase kinase kinase 1 is a protein kinase that in humans is encoded by the ''MAP4K1'' gene. It is also known as HPK1 (Hematopoietic Progenitor Kinase 1). The protein has been shown to play a role in JNK activatio ...

and

Bruton's tyrosine kinase Bruton's tyrosine kinase (abbreviated Btk or BTK), also known as tyrosine-protein kinase BTK, is a tyrosine kinase that is encoded by the ''BTK'' gene in humans. BTK plays a crucial role in B cell development. Structure BTK contains five differ ...

Post-translational modification

References

External links