Protein tyrosine phosphatase
Encyclopedia
Protein tyrosine phosphatases (PTPs) are a group of enzymes that remove phosphate
groups from phosphorylated tyrosine
residues on proteins. Protein tyrosine (pTyr) phosphorylation is a common post-translational modification that can create novel recognition motifs for protein interactions and cellular localisation, affect protein stability, and regulate enzyme activity. As a consequence, maintaining an appropriate level of protein tyrosine phosphorylation is essential for many cellular functions. Tyrosine-specific protein phosphatases (PTPase; ) catalyse the removal of a phosphate group attached to a tyrosine residue, using a cysteinyl-phosphate enzyme intermediate. These enzymes are key regulatory components in signal transduction
pathways (such as the MAP kinase pathway) and cell cycle control, and are important in the control of cell growth, proliferation, differentiation and transformation.
s, PTPs regulate the phosphorylation state of many important signalling molecules, such as the MAP kinase family.
PTPs are increasingly viewed as integral components of signal transduction cascades, despite less study and understanding compared to tyrosine kinase
s.
PTPs have been implicated in regulation of many cellular processes, including, but not limited to:
Links to all 107 members of the protein tyrosine phosphatase family can be found in the template at the bottom of this article.
Dual-specificity phosphatases (dTyr and dSer/dThr) dual-specificity protein-tyrosine phosphatases. Ser/Thr and Tyr dual-specificity phosphatases are a group of enzymes with both Ser/Thr and tyrosine-specific protein phosphatase activity able to remove the serine/threonine or the tyrosine-bound phosphate group from a wide range of phosphoproteins, including a number of enzymes that have been phosphorylated under the action of a kinase. Dual-specificity protein phosphatases (DSPs) regulate mitogenic signal transduction and control the cell cycle.
LEOPARD syndrome
, Noonan syndrome
, and Metachondromatosis
are associated with PTPN11
.
The class II PTPs contain only one member, low-molecular-weight phosphotyrosine phosphatase (LMPTP).
The Class III PTPs contains three members, CDC25 A
, B
, and C
The class IV PTPs contains four members, Eya1-4
.
This class is believed to have evolved separately from the other three.
by all cell types, or their expression may be strictly tissue
-specific. Most cells express 30% to 60% of all the PTPs, however hematopoietic and neuronal cells express a higher number of PTPs in comparison to other cell types. T cell
s and B cell
s of hematopoietic origin express around 60 to 70 different PTPs. The expression of several PTPS is restricted to hematopoietic cells, for example, LYP, SHP1, CD45
, and HePTP.
Phosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...
groups from phosphorylated tyrosine
Tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
residues on proteins. Protein tyrosine (pTyr) phosphorylation is a common post-translational modification that can create novel recognition motifs for protein interactions and cellular localisation, affect protein stability, and regulate enzyme activity. As a consequence, maintaining an appropriate level of protein tyrosine phosphorylation is essential for many cellular functions. Tyrosine-specific protein phosphatases (PTPase; ) catalyse the removal of a phosphate group attached to a tyrosine residue, using a cysteinyl-phosphate enzyme intermediate. These enzymes are key regulatory components in signal transduction
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
pathways (such as the MAP kinase pathway) and cell cycle control, and are important in the control of cell growth, proliferation, differentiation and transformation.
Functions
Together with tyrosine kinaseTyrosine 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....
s, PTPs regulate the phosphorylation state of many important signalling molecules, such as the MAP kinase family.
PTPs are increasingly viewed as integral components of signal transduction cascades, despite less study and understanding compared to 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....
s.
PTPs have been implicated in regulation of many cellular processes, including, but not limited to:
- Cell growthCell growthThe term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"...
- Cellular differentiationCellular differentiationIn developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...
- MitoticMitosisMitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...
cycles - Oncogenic transformation
By mechanism
The PTP superfamily can be divided into four subfamilies.Links to all 107 members of the protein tyrosine phosphatase family can be found in the template at the bottom of this article.
Class I
The class I PTPs, are the largest group of PTPs with 99 members, which can be further subdivided into- 38 classical PTPs
- 21 receptor tyrosine phosphataseReceptor tyrosine phosphataseReceptor tyrosine phosphatase is a type of Enzyme-linked receptor.Types include PTPRA, PTPRB, PTPRC, PTPRD, PTPRE, PTPRF, PTPRG, PTPRH, PTPRJ, PTPRK, PTPRM, PTPRN, PTPRN2, PTPRO, PTPRQ, PTPRR, PTPRS, PTPRT, PTPRU, and PTPRZ....
- 17 nonreceptor-type PTPs
- 21 receptor tyrosine phosphatase
- 61 VH-1-like or dual-specific phosphatases (DSPs)
- 11 MAPK phosphatases (MPKs)
- 3 Slingshots
- 3 PRLs
- 4 CDC14s
- 19 atypical DSPs
- 5 Phosphatase and tensin homologPTEN (gene)Phosphatase and tensin homolog is a protein that, in humans, is encoded by the PTEN gene. Mutations of this gene are a step in the development of many cancers....
s (PTENs) - 16 MyotubularinMyotubularinMyotubularin domain represents a region within eukaryotic myotubularin-related proteins that is sometimes found with . Myotubularin is a dual-specific lipid phosphatase that dephosphorylates phosphatidylinositol 3-phosphate and phosphatidylinositol -bi-phosphate...
s
Dual-specificity phosphatases (dTyr and dSer/dThr) dual-specificity protein-tyrosine phosphatases. Ser/Thr and Tyr dual-specificity phosphatases are a group of enzymes with both Ser/Thr and tyrosine-specific protein phosphatase activity able to remove the serine/threonine or the tyrosine-bound phosphate group from a wide range of phosphoproteins, including a number of enzymes that have been phosphorylated under the action of a kinase. Dual-specificity protein phosphatases (DSPs) regulate mitogenic signal transduction and control the cell cycle.
LEOPARD syndrome
Leopard syndrome
LEOPARD syndrome - is part of a group called Ras/MAPK pathway syndromes - is a rare autosomal dominant, multisystem disease caused by a...
, Noonan syndrome
Noonan syndrome
Noonan Syndrome is a relatively common autosomal dominant congenital disorder considered to be a type of dwarfism, that affects both males and females equally. It used to be referred to as the male version of Turner's syndrome ; however, the genetic causes of Noonan syndrome and Turner syndrome...
, and Metachondromatosis
Metachondromatosis
Metachondromatosis is an autosomal dominant skeletal disorder affecting the growth of bones, leading to multiple enchondromas and osteochondromas. Affects mainly tubular bones, though can involve the vertebrae.-Genetics:...
are associated with PTPN11
PTPN11
Tyrosine-protein phosphatase non-receptor type 11 also known as protein-tyrosine phosphatase 1D or protein-tyrosine phosphatase 2C is an enzyme that in humans is encoded by the PTPN11 gene. PTPN11 is a protein tyrosine phosphatase Shp2.PTPN11 is a member of the protein tyrosine phosphatase ...
.
Class II
LMW (low-molecular-weight) phosphatases, or acid phosphatases act on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates.The class II PTPs contain only one member, low-molecular-weight phosphotyrosine phosphatase (LMPTP).
Class III
Cdc25 phosphatases (dTyr and/or dThr)The Class III PTPs contains three members, CDC25 A
CDC25A
Cell division cycle 25 homolog A , also known as CDC25A, is a mammalian gene.-Interactions:CDC25A has been shown to interact with ASK1, Epidermal growth factor receptor, C-Raf, CHEK1, Cyclin E1, PIM1 and YWHAB.-Further reading:...
, B
CDC25B
M-phase inducer phosphatase 2 is an enzyme that in humans is encoded by the CDC25B gene.-Interactions:CDC25B has been shown to interact with MAPK14, Casein kinase 2, alpha 1, CHEK1, MELK, Estrogen receptor alpha, YWHAB, YWHAZ, YWHAH and YWHAE....
, and C
CDC25C
M-phase inducer phosphatase 3 is an enzyme that in humans is encoded by the CDC25C gene.-Interactions:CDC25C has been shown to interact with MAPK14, CHEK1, PCNA, PIN1, PLK3 and NEDD4.-Further reading:...
Class IV
pTyr-specific phosphatasesThe class IV PTPs contains four members, Eya1-4
EYA1
Eyes absent homolog 1 is a protein that in humans is encoded by the EYA1 gene.-Further reading:...
.
This class is believed to have evolved separately from the other three.
By location
Based on their cellular localization, PTPases are also classified as:- Receptor-like, which are transmembrane receptors that contain PTPase domains. In terms of structure, all known receptor PTPases are made up of a variable-length extracellular domain, followed by a transmembrane region and a C-terminal catalytic cytoplasmic domain. Some of the receptor PTPases contain fibronectin type III (FN-III) repeats, immunoglobulin-like domains, MAM domains, or carbonic anhydrase-like domains in their extracellular region. In general, the cytoplasmic region contains two copies of the PTPase domain. The first seems to have enzymatic activity, whereas the second is inactive.
- Non-receptor (intracellular) PTPases
Common elements
All PTPases carry the highly conserved active site motif C(X)5R (PTP signature motif), employ a common catalytic mechanism, and possess a similar core structure made of a central parallel beta-sheet with flanking alpha-helices containing a beta-loop-alpha-loop that encompasses the PTP signature motif. Functional diversity between PTPases is endowed by regulatory domains and subunits.Expression pattern
Individual PTPs may be expressedGene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
by all cell types, or their expression may be strictly tissue
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
-specific. Most cells express 30% to 60% of all the PTPs, however hematopoietic and neuronal cells express a higher number of PTPs in comparison to other cell types. 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 B cell
B 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 of hematopoietic origin express around 60 to 70 different PTPs. The expression of several PTPS is restricted to hematopoietic cells, for example, LYP, SHP1, CD45
CD45
Protein tyrosine phosphatase, receptor type, C also known as PTPRC is an enzyme that, in humans, is encoded by the PTPRC gene. PTPRC is also known as CD45 antigen , which was originally called leukocyte common antigen.- Function :The protein encoded by this gene is a member of the protein tyrosine...
, and HePTP.
External links
- PTP Summary and Relevant Publications at Monash UniversityMonash UniversityMonash University is a public university based in Melbourne, Victoria. It was founded in 1958 and is the second oldest university in the state. Monash is a member of Australia's Group of Eight and the ASAIHL....