ZAP-70
Encyclopedia
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 cell
s and natural killer cells and has a critical role in the initiation of T-cell signaling.
s is used as a prognostic marker in identifying different forms of chronic lymphocytic leukemia
(CLL).
ZAP70 deficiency
results in a form of immune deficiency.
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 linker of activated T cells
(LAT). 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 cytokine
s.
with Lck
, FYN
, SHB
, LAT
, Cbl gene
, Drebrin-like
and SHC1
.
KDA
KDA may refer to:* Karachi Development Authority* Kongsberg Defence & Aerospace* Kotelawala Defence Academy* Kramer Design Associates* Lithium diisopropylamide, KDA is the potassium analogue of lithium diisopropylamideOr kDa may refer to:...
). The protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
is a member in the protein-tyrosine kinase
Tyrosine kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a protein in a cell. It functions as an "on" or "off" switch in many cellular functions....
family. ZAP-70 is normally expressed in T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
s and natural killer cells and has a critical role in the initiation of T-cell signaling.
Clinical significance
ZAP-70 in B cellB cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...
s is used as a prognostic marker in identifying different forms of chronic lymphocytic leukemia
Chronic lymphocytic leukemia
B-cell chronic lymphocytic leukemia , also known as chronic lymphoid leukemia , is the most common type of leukemia. Leukemias are cancers of the white blood cells . CLL affects B cell lymphocytes. B cells originate in the bone marrow, develop in the lymph nodes, and normally fight infection by...
(CLL).
ZAP70 deficiency
ZAP70 deficiency
ZAP70 deficiency, or zeta-chain-associated protein 70 kD deficiency, is a rare autosomal recessive form of severe combined immunodeficiency .It is associated with ZAP70.-Presentation:...
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 LckLck
Lck is a protein that is found inside specialized cells of the immune system called lymphocytes. Lck is a tyrosine kinase, which phosphorylates tyrosine residues of certain proteins involved in the intracellular signaling pathways of these lymphocytes...
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 linker of activated T cells
Linker of activated T cells
Linker of Activated T cells, also known as LAT, is a protein which in humans is encoded by the LAT gene. Alternative splicing results in multiple transcript variants encoding different isoforms.-Function:...
(LAT). 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 cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s.
Interactions
ZAP-70 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with Lck
Lck
Lck is a protein that is found inside specialized cells of the immune system called lymphocytes. Lck is a tyrosine kinase, which phosphorylates tyrosine residues of certain proteins involved in the intracellular signaling pathways of these lymphocytes...
, FYN
FYN
Proto-oncogene tyrosine-protein kinase Fyn is an enzyme that in humans is encoded by the FYN gene.This gene is a member of the protein-tyrosine kinase oncogene family. It encodes a membrane-associated tyrosine kinase that has been implicated in the control of cell growth...
, SHB
SHB (gene)
SH2 domain-containing adapter protein B is a protein that in humans is encoded by the SHB gene.-Interactions:SHB has been shown to interact with Fibroblast growth factor receptor 1, Src, Linker of activated T cells, Lymphocyte cytosolic protein 2, ZAP-70, EPS8, PIK3R1 and VAV1.-Further reading:...
, LAT
Linker of activated T cells
Linker of Activated T cells, also known as LAT, is a protein which in humans is encoded by the LAT gene. Alternative splicing results in multiple transcript variants encoding different isoforms.-Function:...
, Cbl gene
Cbl gene
Cbl is a mammalian gene encoding several proteins including E3 ubiquitin-protein ligase CBL involved in cell signalling and protein ubiquitination...
, Drebrin-like
Drebrin-like
Drebrin-like protein is a protein that in humans is encoded by the DBNL gene.-Interactions:Drebrin-like has been shown to interact with Cyclin-dependent kinase 4, MAP4K1 and ZAP-70.-Further reading:...
and SHC1
SHC1
SHC-transforming protein 1 is a protein that in humans is encoded by the SHC1 gene. SHC has been found to be important in the regulation of apoptosis and drug resistance in mammalian cells....
.