FYB — Mediated Wiki

{{Short description|Protein-coding gene in the species Homo sapiens}}{{About|the protein-coding gene|the Poppy song|Stagger (EP)}}{{Infobox_gene}} '''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 ''FYB'' gene in humans.<ref name="entrez">{{cite web | title = Entrez Gene: FYB FYN binding protein (FYB-120/130)| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=2533}}</ref> The protein is expressed in T cells, monocytes, mast cells, macrophages, NK cells, but not B cells.<ref>{{cite journal | vauthors = Schraven B, Marie-Cardine A, Koretzky G | title = 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 | journal = Immunology Letters | volume = 57 | issue = 1–3 | pages = 165–169 | date = June 1997 | pmid = 9232446 | doi = 10.1016/s0165-2478(97)00053-9 }}</ref><ref name=":0">{{cite journal | vauthors = Griffiths EK, Penninger JM | title = Communication between the TCR and integrins: role of the molecular adapter ADAP/Fyb/Slap | journal = Current Opinion in Immunology | volume = 14 | issue = 3 | pages = 317–322 | date = June 2002 | pmid = 11973129 | doi = 10.1016/s0952-7915(02)00334-5 }}</ref><ref name=":1">{{cite journal | vauthors = Wang H, Rudd CE | title = SKAP-55, SKAP-55-related and ADAP adaptors modulate integrin-mediated immune-cell adhesion | journal = Trends in Cell Biology | volume = 18 | issue = 10 | pages = 486–493 | date = October 2008 | pmid = 18760924 | doi = 10.1016/j.tcb.2008.07.005 | pmc = 3512129 }}</ref><ref name=":2">{{cite journal | vauthors = Gerbec ZJ, Thakar MS, Malarkannan S | title = The Fyn-ADAP Axis: Cytotoxicity Versus Cytokine Production in Killer Cells | journal = Frontiers in Immunology | volume = 6 | page = 472 | date = 2015-09-16 | pmid = 26441977 | doi = 10.3389/fimmu.2015.00472 | pmc = 4584950 | doi-access = free }}</ref> FYB is a multifunctional protein involved in post-activation T cell signaling, lymphocyte cytokine production, cell adhesion, and actin remodeling.<ref name=":0" /><ref name=":1" /><ref name=":2" /><ref name=":3">{{cite journal | vauthors = Zhang Y, Wang H | title = Integrin signalling and function in immune cells | journal = Immunology | volume = 135 | issue = 4 | pages = 268–275 | date = April 2012 | pmid = 22211918 | doi = 10.1111/j.1365-2567.2011.03549.x | pmc = 3372743 }}</ref><ref name=":4">{{cite journal | vauthors = Dadwal N, Mix C, Reinhold A, Witte A, Freund C, Schraven B, Kliche S | title = The Multiple Roles of the Cytosolic Adapter Proteins ADAP, SKAP1 and SKAP2 for TCR/CD3 -Mediated Signaling Events | journal = Frontiers in Immunology | volume = 12 | article-number = 703534 | date = 2021-07-06 | pmid = 34295339 | doi = 10.3389/fimmu.2021.703534 | pmc = 8290198 | doi-access = free }}</ref>

== Structure == Two isoforms of FYB with different lengths of 120 and 130 kDa (FYB-120 and FYB-130) exist.<ref name=":1" /> The 130kDa version has an extra insertion of 46 amino acids and is preferentially expressed in peripheral T cells.<ref name=":1" /> 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.<ref name=":4" />

== Function == 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+).<ref name=":4" />

FYB regulates cytokine production in T cells as well as in activated NK cells through the FYN-ADAP axis.<ref name=":2" /> In T cells, after TCR stimulation, a unique region of FYB, pYDGI, allows phosphorylation of the protein by FYN.<ref name=":2" /> After being phosphorylated, ADAP can bind to Carma1, causing NF-κB translocation into the nucleus and cytokine production.<ref name=":2" />

In mast cells, FYB regulates cell adhesion as well as degranulation.<ref name=":0" /> In T cells, FYB allows for cell adhesion and migration through blood vessels through the SLP-76-FYB-SKAP1 complex.<ref name=":3" /> After being phosphorylated by FYN, FYB can bind to SLP-76.<ref name=":0" /> 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.<ref name=":3" /> FYB can also bind to SKAP1, which allows SKAP1 to upregulate integrin activity through interactions with Rap1.<ref name=":1" /><ref name=":3" /> 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.<ref name=":1" />

FYB is also an important protein for actin remodeling of immune cells.<ref name=":4" /> This is thought to occur through the binding of proteins of the ENA/VASP protein family to the FPPPP-motif of the FYB protein.<ref name=":4" />

== References == {{reflist}}

== Further reading == {{refbegin | 2}} * {{cite journal | vauthors = da Silva AJ, Janssen O, Rudd CE | title = T cell receptor zeta/CD3-p59fyn(T)-associated p120/130 binds to the SH2 domain of p59fyn(T) | journal = The Journal of Experimental Medicine | volume = 178 | issue = 6 | pages = 2107–2113 | date = December 1993 | pmid = 7504057 | pmc = 2191307 | doi = 10.1084/jem.178.6.2107 }} * {{cite journal | vauthors = Musci MA, Hendricks-Taylor LR, Motto DG, Paskind M, Kamens J, Turck CW, Koretzky GA | title = Molecular cloning of SLAP-130, an SLP-76-associated substrate of the T cell antigen receptor-stimulated protein tyrosine kinases | journal = The Journal of Biological Chemistry | volume = 272 | issue = 18 | pages = 11674–11677 | date = May 1997 | pmid = 9115214 | doi = 10.1074/jbc.272.18.11674 | doi-access = free }} * {{cite journal | vauthors = da Silva AJ, Li Z, de Vera C, Canto E, Findell P, Rudd CE | title = Cloning of a novel T-cell protein FYB that binds FYN and SH2-domain-containing leukocyte protein 76 and modulates interleukin 2 production | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 14 | pages = 7493–7498 | date = July 1997 | pmid = 9207119 | pmc = 23849 | doi = 10.1073/pnas.94.14.7493 | doi-access = free | bibcode = 1997PNAS...94.7493D }} * {{cite journal | vauthors = Liu J, Kang H, Raab M, da Silva AJ, Kraeft SK, Rudd CE | title = FYB (FYN binding protein) serves as a binding partner for lymphoid protein and FYN kinase substrate SKAP55 and a SKAP55-related protein in T cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 15 | pages = 8779–8784 | date = July 1998 | pmid = 9671755 | pmc = 21153 | doi = 10.1073/pnas.95.15.8779 | doi-access = free | bibcode = 1998PNAS...95.8779L }} * {{cite journal | vauthors = Marie-Cardine A, Hendricks-Taylor LR, Boerth NJ, Zhao H, Schraven B, Koretzky GA | title = Molecular interaction between the Fyn-associated protein SKAP55 and the SLP-76-associated phosphoprotein SLAP-130 | journal = The Journal of Biological Chemistry | volume = 273 | issue = 40 | pages = 25789–25795 | date = October 1998 | pmid = 9748251 | doi = 10.1074/jbc.273.40.25789 | doi-access = free }} * {{cite journal | vauthors = Marie-Cardine A, Verhagen AM, Eckerskorn C, Schraven B | title = SKAP-HOM, a novel adaptor protein homologous to the FYN-associated protein SKAP55 | journal = FEBS Letters | volume = 435 | issue = 1 | pages = 55–60 | date = September 1998 | pmid = 9755858 | doi = 10.1016/S0014-5793(98)01040-0 | s2cid = 37288744 | doi-access = free }} * {{cite journal | vauthors = Veale M, Raab M, Li Z, da Silva AJ, Kraeft SK, Weremowicz S, Morton CC, Rudd CE | display-authors = 6 | title = Novel isoform of lymphoid adaptor FYN-T-binding protein (FYB-130) interacts with SLP-76 and up-regulates interleukin 2 production | journal = The Journal of Biological Chemistry | volume = 274 | issue = 40 | pages = 28427–28435 | date = October 1999 | pmid = 10497204 | doi = 10.1074/jbc.274.40.28427 | doi-access = free }} * {{cite journal | vauthors = Hamid N, Gustavsson A, Andersson K, McGee K, Persson C, Rudd CE, Fällman M | title = YopH dephosphorylates Cas and Fyn-binding protein in macrophages | journal = Microbial Pathogenesis | volume = 27 | issue = 4 | pages = 231–242 | date = October 1999 | pmid = 10502464 | doi = 10.1006/mpat.1999.0301 }} * {{cite journal | vauthors = Geng L, Raab M, Rudd CE | title = Cutting edge: SLP-76 cooperativity with FYB/FYN-T in the Up-regulation of TCR-driven IL-2 transcription requires SLP-76 binding to FYB at Tyr595 and Tyr651 | journal = Journal of Immunology | volume = 163 | issue = 11 | pages = 5753–5757 | date = December 1999 | doi = 10.4049/jimmunol.163.11.5753 | pmid = 10570256 | s2cid = 29719649 | doi-access = free }} * {{cite journal | vauthors = Krause M, Sechi AS, Konradt M, Monner D, Gertler FB, Wehland J | title = Fyn-binding protein (Fyb)/SLP-76-associated protein (SLAP), Ena/vasodilator-stimulated phosphoprotein (VASP) proteins and the Arp2/3 complex link T cell receptor (TCR) signaling to the actin cytoskeleton | journal = The Journal of Cell Biology | volume = 149 | issue = 1 | pages = 181–194 | date = April 2000 | pmid = 10747096 | pmc = 2175102 | doi = 10.1083/jcb.149.1.181 }} * {{cite journal | vauthors = Kang H, Freund C, Duke-Cohan JS, Musacchio A, Wagner G, Rudd CE | title = SH3 domain recognition of a proline-independent tyrosine-based RKxxYxxY motif in immune cell adaptor SKAP55 | journal = The EMBO Journal | volume = 19 | issue = 12 | pages = 2889–2899 | date = June 2000 | pmid = 10856234 | pmc = 203341 | doi = 10.1093/emboj/19.12.2889 }} * {{cite journal | vauthors = Asazuma N, Wilde JI, Berlanga O, Leduc M, Leo A, Schweighoffer E, Tybulewicz V, Bon C, Liu SK, McGlade CJ, Schraven B, Watson SP | display-authors = 6 | title = Interaction of linker for activation of T cells with multiple adapter proteins in platelets activated by the glycoprotein VI-selective ligand, convulxin | journal = The Journal of Biological Chemistry | volume = 275 | issue = 43 | pages = 33427–33434 | date = October 2000 | pmid = 10942756 | doi = 10.1074/jbc.M001439200 | doi-access = free }} * {{cite journal | vauthors = Li C, Iosef C, Jia CY, Han VK, Li SS | title = Dual functional roles for the X-linked lymphoproliferative syndrome gene product SAP/SH2D1A in signaling through the signaling lymphocyte activation molecule (SLAM) family of immune receptors | journal = The Journal of Biological Chemistry | volume = 278 | issue = 6 | pages = 3852–3859 | date = February 2003 | pmid = 12458214 | doi = 10.1074/jbc.M206649200 | doi-access = free }} * {{cite journal | vauthors = Brill LM, Salomon AR, Ficarro SB, Mukherji M, Stettler-Gill M, Peters EC | title = Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry | journal = Analytical Chemistry | volume = 76 | issue = 10 | pages = 2763–2772 | date = May 2004 | pmid = 15144186 | doi = 10.1021/ac035352d }} * {{cite journal | vauthors = Heuer K, Arbuzova A, Strauss H, Kofler M, Freund C | title = The helically extended SH3 domain of the T cell adaptor protein ADAP is a novel lipid interaction domain | journal = Journal of Molecular Biology | volume = 348 | issue = 4 | pages = 1025–1035 | date = May 2005 | pmid = 15843031 | doi = 10.1016/j.jmb.2005.02.069 }} * {{cite journal | vauthors = Huang Y, Norton DD, Precht P, Martindale JL, Burkhardt JK, Wange RL | title = Deficiency of ADAP/Fyb/SLAP-130 destabilizes SKAP55 in Jurkat T cells | journal = The Journal of Biological Chemistry | volume = 280 | issue = 25 | pages = 23576–23583 | date = June 2005 | pmid = 15849195 | doi = 10.1074/jbc.M413201200 | doi-access = free }} * {{cite journal | vauthors = Koga S, Yogo K, Yoshikawa K, Samori H, Goto M, Uchida T, Ishida N, Takeya T | display-authors = 6 | title = Physical and functional association of c-Src and adhesion and degranulation promoting adaptor protein (ADAP) in osteoclastogenesis in vitro | journal = The Journal of Biological Chemistry | volume = 280 | issue = 36 | pages = 31564–31571 | date = September 2005 | pmid = 16020549 | doi = 10.1074/jbc.M502703200 | doi-access = free }} * {{cite journal | vauthors = Duke-Cohan JS, Kang H, Liu H, Rudd CE | title = Regulation and function of SKAP-55 non-canonical motif binding to the SH3c domain of adhesion and degranulation-promoting adaptor protein | journal = The Journal of Biological Chemistry | volume = 281 | issue = 19 | pages = 13743–13750 | date = May 2006 | pmid = 16461356 | doi = 10.1074/jbc.M508774200 | doi-access = free }} {{refend}}