FYN binding protein (FYB-120/130), also known as FYB, ADAP (Adhesion and degranulation-promoting adapter protein), and SLAP-130 ( SLP-76-associated phosphoprotein) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that is encoded by the ''FYB''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

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 produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

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_junction, cell junc ...

, and

actin remodeling Actin is a protein family, family of Globular protein, globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in myofibril, muscle fibrils. It is found in essentially all Eukaryote, eukaryotic cel ...

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 and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have uniqu ...

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 ph ...

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 (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 addit ...

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 ...

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 Proto-oncogene tyrosine-protein kinase Fyn (p59-FYN, Slk, Syn, MGC45350, Gene ID 2534) is an enzyme that in humans is encoded by the ''FYN'' gene. Fyn is a 59-kDa member of the Src family of kinases typically associated with T-cell and neurona ...

. 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 family of transcription factor protein complexes that controls transcription (genetics), transcription of DNA, cytokine production and cell survival. NF-κB is found i ...

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 SLP-76-FYB-

SKAP1 Src kinase-associated phosphoprotein 1 is an adapter protein that in humans is encoded by the ''SKAP1'' gene. This gene encodes a T cell adapter protein, a class of intracellular molecules with modular domains capable of recruiting additional pr ...

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 help 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, o ...

. 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 '' ...

'' 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