FYN binding protein (FYB-120/130), also known as FYB, ADAP (Adhesion and degranulation-promoting adapter protein), and SLAP-130 (

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 ...

-associated phosphoprotein) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that is encoded by the ''FYB''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

in humans. The protein is expressed in T cells, monocytes, mast cells, macrophages, NK cells, but not B cells. FYB is a multifunctional protein involved in post-activation T cell signaling, lymphocyte

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

production,

cell adhesion Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as cell junctions or indir ...

, and

actin remodeling Actin remodeling is the biochemical process that allows for the dynamic alterations of cellular organization. The remodeling of actin filaments occurs in a cyclic pattern on cell surfaces and exists as a fundamental aspect to cellular life. Durin ...

Structure

Two

isoforms A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...

of FYB with different lengths of 120 and 130 kDa (FYB-120 and FYB-130) exist. The 130kDa version has an extra insertion of 46 amino acids and is preferentially expressed in peripheral T cells. The FYB protein has a variety of binding domains: a non-structured N-terminal region, a proline-rich region, two

SH3 domain The SRC Homology 3 Domain (or SH3 domain) is a small protein domain of about 60 amino acid residues. Initially, SH3 was described as a conserved sequence in the viral adaptor protein v-Crk. This domain is also present in the molecules of phos ...

s, a FPPP-motif which binds the ENA/VASP protein family, and other tyrosine-based signaling motifs.

Function

FYB is critical for activation and proliferation of

T-helper cells The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are consider ...

(CD4+) and required for

chemokine Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In additio ...

signal transduction in T-helper cells and

cytotoxic T cell A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pa ...

s (CD8+). FYB regulates

production in T cells as well as in activated NK cells through the FYN-ADAP axis. In T cells, after TCR stimulation, a unique region of FYB, pYDGI, allows phosphorylation of the protein by

FYN Funen ( da, Fyn, ), with an area of , is the third-largest island of Denmark, after Zealand and Vendsyssel-Thy. It is the 165th-largest island in the world. It is located in the central part of the country and has a population of 469,947 as of ...

. After being phosphorylated, ADAP can bind to Carma1, causing

NF-κB Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular ...

translocation into the nucleus and cytokine production. In mast cells, FYB regulates cell adhesion as well as degranulation. In T cells, FYB allows for cell adhesion and migration through blood vessels through the

-FYB- SKAP1 complex. After being phosphorylated by FYN, FYB can bind to SLP-76. This binding of FYB and SLP-76 regulates "outside-in signaling" or the transfer of signals from outside the cell to inside the cell by

integrin Integrins are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, ...

. FYB can also bind to SKAP1, which allows SKAP1 to upregulate integrin activity through interactions with

Rap1 Rap1 (Ras-proximate-1 or Ras-related protein 1) is a small GTPase, which are small cytosolic proteins that act like cellular switches and are vital for effective signal transduction. There are two isoforms of the Rap1 protein, each encoded by ...

. The bacteria ''

Yersinia ''Yersinia'' is a genus of bacteria in the family Yersiniaceae. ''Yersinia'' species are Gram-negative, coccobacilli bacteria, a few micrometers long and fractions of a micrometer in diameter, and are facultative anaerobes. Some members of ''Ye ...

'' can interfere with this pathway in macrophages through the secretion of YopH (''Yersinia'' protein tyrosine phosphatase) into the macrophage, which de-phosphorylates FYB and SKAP1, leading to a decrease in integrin activity that results in an inhibition of adhesion, phagocytosis, and cytotoxicity. FYB is also an important protein for

of immune cells. This is thought to occur through the binding of proteins of the ENA/VASP protein family to the FPPPP-motif of the FYB protein.

Structure

Function

References

Further reading