ZAP-70

ZAP-70

ZAP-70 is an abbreviation for Zeta-chain-associated protein kinase 70 (70 is the molecular weight in kDa). The protein is a member in the protein-tyrosine kinase family. ZAP-70 is normally expressed in T cells and natural killer cells and has a critical role in the initiation of T-cell signaling.

Clinical significance

ZAP-70 in B cells is used as a prognostic marker in identifying different forms of chronic lymphocytic leukemia (CLL).

ZAP70 deficiency results in a form of immune deficiency.

Function

T lymphocytes are activated by engagement of the T cell receptor with processed antigen fragments presented by professional antigen presenting cells (e.g. macrophages, dendritic cells and B cells). Upon this activation, the tyrosine kinase Lck becomes activated and phosphorylates the intracellular portions of the CD3 complex (called ITAMs). The most important member of the CD3 family is CD3-zeta to which ZAP-70 binds (hence the abbreviation). The tandem SH2-domains of ZAP-70 are engaged by the doubly phosphorylated ITAMs of CD3-zeta, which positions ZAP-70 to phosphorylate the transmembrane protein LAT (Linker of Activated T cells). Phosphorylated LAT in turn serves as a docking site to which a number of signaling proteins bind. The final outcome of T cell activation is the transcription of several gene products which allow the T cells to differentiate, proliferate and secrete a number of cytokines.

ee also

* Lck
* Syk

Further reading

*
*PBB_Further_reading
citations =
*cite journal | author=Orchard J, Ibbotson R, Best G, "et al." |title=ZAP-70 in B cell malignancies. |journal=Leuk. Lymphoma |volume=46 |issue= 12 |pages= 1689–98 |year= 2006 |pmid= 16263570 |doi= 10.1080/09638280500260079
*cite journal | author=Hamblin AD, Hamblin TJ |title=Functional and prognostic role of ZAP-70 in chronic lymphocytic leukaemia. |journal=Expert Opin. Ther. Targets |volume=9 |issue= 6 |pages= 1165–78 |year= 2006 |pmid= 16300468 |doi= 10.1517/14728222.9.6.1165
*cite journal | author=Chan AC, Iwashima M, Turck CW, Weiss A |title=ZAP-70: a 70 kd protein-tyrosine kinase that associates with the TCR zeta chain. |journal=Cell |volume=71 |issue= 4 |pages= 649–62 |year= 1992 |pmid= 1423621 |doi=
*cite journal | author=Goldman F, Jensen WA, Johnson GL, "et al." |title=gp120 ligation of CD4 induces p56lck activation and TCR desensitization independent of TCR tyrosine phosphorylation. |journal=J. Immunol. |volume=153 |issue= 7 |pages= 2905–17 |year= 1994 |pmid= 7522245 |doi=
*cite journal | author=Isakov N, Wange RL, Burgess WH, "et al." |title=ZAP-70 binding specificity to T cell receptor tyrosine-based activation motifs: the tandem SH2 domains of ZAP-70 bind distinct tyrosine-based activation motifs with varying affinity. |journal=J. Exp. Med. |volume=181 |issue= 1 |pages= 375–80 |year= 1995 |pmid= 7528772 |doi=
*cite journal | author=Nel AE, Gupta S, Lee L, "et al." |title=Ligation of the T-cell antigen receptor (TCR) induces association of hSos1, ZAP-70, phospholipase C-gamma 1, and other phosphoproteins with Grb2 and the zeta-chain of the TCR. |journal=J. Biol. Chem. |volume=270 |issue= 31 |pages= 18428–36 |year= 1995 |pmid= 7629168 |doi=
*cite journal | author=Negishi I, Motoyama N, Nakayama K, "et al." |title=Essential role for ZAP-70 in both positive and negative selection of thymocytes. |journal=Nature |volume=376 |issue= 6539 |pages= 435–8 |year= 1995 |pmid= 7630421 |doi= 10.1038/376435a0
*cite journal | author=Mustelin T, Williams S, Tailor P, "et al." |title=Regulation of the p70zap tyrosine protein kinase in T cells by the CD45 phosphotyrosine phosphatase. |journal=Eur. J. Immunol. |volume=25 |issue= 4 |pages= 942–6 |year= 1995 |pmid= 7737297 |doi=
*cite journal | author=Neumeister EN, Zhu Y, Richard S, "et al." |title=Binding of ZAP-70 to phosphorylated T-cell receptor zeta and eta enhances its autophosphorylation and generates specific binding sites for SH2 domain-containing proteins. |journal=Mol. Cell. Biol. |volume=15 |issue= 6 |pages= 3171–8 |year= 1995 |pmid= 7760813 |doi=
*cite journal | author=Katzav S, Sutherland M, Packham G, "et al." |title=The protein tyrosine kinase ZAP-70 can associate with the SH2 domain of proto-Vav. |journal=J. Biol. Chem. |volume=269 |issue= 51 |pages= 32579–85 |year= 1995 |pmid= 7798261 |doi=
*cite journal | author=Schumann G, Dasgupta JD |title=Specificity of signal transduction through CD16, TCR-CD3 and BCR receptor chains containing the tyrosine-associated activation motif. |journal=Int. Immunol. |volume=6 |issue= 9 |pages= 1383–92 |year= 1995 |pmid= 7819147 |doi=
*cite journal | author=Watts JD, Affolter M, Krebs DL, "et al." |title=Identification by electrospray ionization mass spectrometry of the sites of tyrosine phosphorylation induced in activated Jurkat T cells on the protein tyrosine kinase ZAP-70. |journal=J. Biol. Chem. |volume=269 |issue= 47 |pages= 29520–9 |year= 1994 |pmid= 7961936 |doi=
*cite journal | author=Ku G, Malissen B, Mattei MG |title=Chromosomal location of the Syk and ZAP-70 tyrosine kinase genes in mice and humans. |journal=Immunogenetics |volume=40 |issue= 4 |pages= 300–2 |year= 1994 |pmid= 8082894 |doi=
*cite journal | author=Chan AC, van Oers NS, Tran A, "et al." |title=Differential expression of ZAP-70 and Syk protein tyrosine kinases, and the role of this family of protein tyrosine kinases in TCR signaling. |journal=J. Immunol. |volume=152 |issue= 10 |pages= 4758–66 |year= 1994 |pmid= 8176201 |doi=
*cite journal | author=Elder ME, Lin D, Clever J, "et al." |title=Human severe combined immunodeficiency due to a defect in ZAP-70, a T cell tyrosine kinase. |journal=Science |volume=264 |issue= 5165 |pages= 1596–9 |year= 1994 |pmid= 8202712 |doi=
*cite journal | author=Chan AC, Kadlecek TA, Elder ME, "et al." |title=ZAP-70 deficiency in an autosomal recessive form of severe combined immunodeficiency. |journal=Science |volume=264 |issue= 5165 |pages= 1599–601 |year= 1994 |pmid= 8202713 |doi=
*cite journal | author=Wange RL, Malek SN, Desiderio S, Samelson LE |title=Tandem SH2 domains of ZAP-70 bind to T cell antigen receptor zeta and CD3 epsilon from activated Jurkat T cells. |journal=J. Biol. Chem. |volume=268 |issue= 26 |pages= 19797–801 |year= 1993 |pmid= 8366117 |doi=
*cite journal | author=Huby RD, Carlile GW, Ley SC |title=Interactions between the protein-tyrosine kinase ZAP-70, the proto-oncoprotein Vav, and tubulin in Jurkat T cells. |journal=J. Biol. Chem. |volume=270 |issue= 51 |pages= 30241–4 |year= 1996 |pmid= 8530437 |doi=
*cite journal | author=Plas DR, Johnson R, Pingel JT, "et al." |title=Direct regulation of ZAP-70 by SHP-1 in T cell antigen receptor signaling. |journal=Science |volume=272 |issue= 5265 |pages= 1173–6 |year= 1996 |pmid= 8638162 |doi=
*cite journal | author=Wardenburg JB, Fu C, Jackman JK, "et al." |title=Phosphorylation of SLP-76 by the ZAP-70 protein-tyrosine kinase is required for T-cell receptor function. |journal=J. Biol. Chem. |volume=271 |issue= 33 |pages= 19641–4 |year= 1996 |pmid= 8702662 |doi=

External links

*

PBB_Controls
update_page = yes
require_manual_inspection = no
update_protein_box = yes
update_summary = no
update_citations = yes


Wikimedia Foundation. 2010.

См. также в других словарях:

  • Zap — can refer to:* An onomatopoeia, referring to electricity * Zap Comix, a series of underground comics * Zap, North Dakota * Zap! (computer game) * Zap (song) is the name of the instrumental song by Eric Johnson * Raye Hollitt, a cast member on… …   Wikipedia

  • ZAP — Cette page d’homonymie répertorie les différents sujets et articles partageant un même nom. Zap peut faire référence à : Zap, un projet qui vise a ajouter une pile Session Initiation Protocol (SIP) à la base de Mozilla, Zap, une série… …   Wikipédia en Français

  • Zap — puede referirse a: Zap (LGBT), una forma de acción pro LGBT. Zap (Dakota del Norte), una pequeña ciudad en el estado estadounidense de Dakota del Norte. Zap Comix, una publicación emblemática del cómic underground. Zap 210 es un personaje de… …   Wikipedia Español

  • ZAP — steht als Abkürzung für: Zentrale Prüfungen am Ende der Klasse 10 ZAP (Fahrzeughersteller), Fahrzeughersteller ZAP Verlag, juristischer Fachverlag, der der LexisNexis Deutschland GmbH angeschlossen ist. ZAP Fanzine, ein deutsches Hardcore Punk… …   Deutsch Wikipedia

  • zap — [zæp] v past tense and past participle zapped present participle zapping informal [Date: 1900 2000; Origin: From the sound of a sudden sharp blow] 1.) [T] to quickly attack or destroy something, especially using a beam of electricity ▪ Doctors… …   Dictionary of contemporary English

  • Zap — Zap, ND U.S. city in North Dakota Population (2000): 231 Housing Units (2000): 129 Land area (2000): 1.041613 sq. miles (2.697764 sq. km) Water area (2000): 0.000000 sq. miles (0.000000 sq. km) Total area (2000): 1.041613 sq. miles (2.697764 sq.… …   StarDict's U.S. Gazetteer Places

  • Zap, ND — U.S. city in North Dakota Population (2000): 231 Housing Units (2000): 129 Land area (2000): 1.041613 sq. miles (2.697764 sq. km) Water area (2000): 0.000000 sq. miles (0.000000 sq. km) Total area (2000): 1.041613 sq. miles (2.697764 sq. km) FIPS …   StarDict's U.S. Gazetteer Places

  • zap — zap; zap·per; zap·o·did; …   English syllables

  • zap — (z[a^]p), v. t. 1. to shoot, destroy, or inactivate; my TV set was zapped by lightning. [PJC] 2. to bomb with an atomic bomb. Syn: nuke, atomize. [WordNet 1.5] 3. to cook or heat in a microwave oven. Syn: microwave, micro cook, nuke. [WordNet… …   The Collaborative International Dictionary of English

  • ZAP — TV es una empresa chilena de televisión satelital que pertenece en partes iguales a Telefonica CTC Chile y la ANFP. ZAP ofrece una gran variedad de canales de diferentes géneros, aunque aún no con gran cantidad así como DirecTV o DISH Network,… …   Enciclopedia Universal


Поделиться ссылкой на выделенное

Прямая ссылка:
Нажмите правой клавишей мыши и выберите «Копировать ссылку»