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FYB

From Wikipedia, the free encyclopedia
Fyb
Identifiers
Aliases
External IDsGeneCards:
Orthologs
DatabasesNCBI: entry; OMA: entry
SpeciesHumanMouse
Entrez

23880

n/a

Ensembl

ENSMUSG00000022148

n/a

UniProt

O35601

O35601

RefSeq (mRNA)

NM_001278269
NM_011815

n/a

RefSeq (protein)

NP_001265198
NP_035945

NP_001265198
NP_035945

Location (UCSC)Chr 15: 6.55 – 6.69 Mbn/a
PubMed search[1]n/a
Wikidata
View/Edit Human

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 that is encoded by the FYB1 gene in humans (previously FYB).[2] The protein is expressed in T cells, monocytes, mast cells, macrophages, NK cells, but not B cells.[3][4][5][6] FYB is a multifunctional protein involved in post-activation T cell signaling, lymphocyte cytokine production, cell adhesion, and actin remodeling.[4][5][6][7][8]

Structure

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Two isoforms of FYB with different lengths of 120 and 130 kDa (FYB-120 and FYB-130) exist.[5] The 130kDa version has an extra insertion of 46 amino acids and is preferentially expressed in peripheral T cells.[5] The FYB protein has a variety of binding domains: a non-structured N-terminal region, a proline-rich region, two SH3 domains, a FPPP-motif which binds the ENA/VASP protein family, and other tyrosine-based signaling motifs.[8]

Function

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FYB is critical for activation and proliferation of T-helper cells (CD4+) and required for chemokine signal transduction in T-helper cells and cytotoxic T cells (CD8+).[8]

FYB regulates cytokine production in T cells as well as in activated NK cells through the FYN-ADAP axis.[6] In T cells, after TCR stimulation, a unique region of FYB, pYDGI, allows phosphorylation of the protein by FYN.[6] After being phosphorylated, ADAP can bind to Carma1, causing NF-κB translocation into the nucleus and cytokine production.[6]

In mast cells, FYB regulates cell adhesion as well as degranulation.[4] In T cells, FYB allows for cell adhesion and migration through blood vessels through the SLP-76-FYB-SKAP1 complex.[7] After being phosphorylated by FYN, FYB can bind to SLP-76.[4] 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.[7] FYB can also bind to SKAP1, which allows SKAP1 to upregulate integrin activity through interactions with Rap1.[5][7] The bacteria Yersinia 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.[5]

FYB is also an important protein for actin remodeling of immune cells.[8] This is thought to occur through the binding of proteins of the ENA/VASP protein family to the FPPPP-motif of the FYB protein.[8]

References

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  1. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  2. ↑ "Entrez Gene: FYB FYN binding protein (FYB-120/130)".
  3. ↑ Schraven B, Marie-Cardine A, Koretzky G (June 1997). "Molecular analysis of the fyn-complex: cloning of SKAP55 and SLAP-130, two novel adaptor proteins which associate with fyn and may participate in the regulation of T cell receptor-mediated signaling". Immunology Letters. 57 (1–3): 165–169. doi:10.1016/s0165-2478(97)00053-9. PMID 9232446.
  4. 1 2 3 4 Griffiths EK, Penninger JM (June 2002). "Communication between the TCR and integrins: role of the molecular adapter ADAP/Fyb/Slap". Current Opinion in Immunology. 14 (3): 317–322. doi:10.1016/s0952-7915(02)00334-5. PMID 11973129.
  5. 1 2 3 4 5 6 Wang H, Rudd CE (October 2008). "SKAP-55, SKAP-55-related and ADAP adaptors modulate integrin-mediated immune-cell adhesion". Trends in Cell Biology. 18 (10): 486–493. doi:10.1016/j.tcb.2008.07.005. PMC 3512129. PMID 18760924.
  6. 1 2 3 4 5 Gerbec ZJ, Thakar MS, Malarkannan S (2015-09-16). "The Fyn-ADAP Axis: Cytotoxicity Versus Cytokine Production in Killer Cells". Frontiers in Immunology. 6: 472. doi:10.3389/fimmu.2015.00472. PMC 4584950. PMID 26441977.
  7. 1 2 3 4 Zhang Y, Wang H (April 2012). "Integrin signalling and function in immune cells". Immunology. 135 (4): 268–275. doi:10.1111/j.1365-2567.2011.03549.x. PMC 3372743. PMID 22211918.
  8. 1 2 3 4 5 Dadwal N, Mix C, Reinhold A, Witte A, Freund C, Schraven B, Kliche S (2021-07-06). "The Multiple Roles of the Cytosolic Adapter Proteins ADAP, SKAP1 and SKAP2 for TCR/CD3 -Mediated Signaling Events". Frontiers in Immunology. 12 703534. doi:10.3389/fimmu.2021.703534. PMC 8290198. PMID 34295339.

Further reading

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Retrieved from "https://en.wikipedia.org/w/index.php?title=FYB&oldid=1367211176"