Together with tyrosine kinases, 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 kinases. PTPs have been implicated in regulation of many cellular processes, including, but not limited to:
Cell growth
Cellular differentiation
Mitotic cycles
Oncogenic transformation
Receptor endocytosis
Classification
By mechanism
PTP activity can be found in four protein families. Links to all 107 members of the protein tyrosine phosphatase family can be found in the 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
Dual-specificity phosphatases 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 regulate mitogenic signal transduction and control the cell cycle. LEOPARD syndrome, Noonan syndrome, and Metachondromatosis are associated with PTPN11. Elevated levels of activated PTPN5 negatively affects synaptic stability and plays a role in Alzheimer’s disease, Fragile X Syndromeschizophrenia, and Parkinson’s disease. Decreased levels of PTPN5 has been implicated in Huntington's disease, cerebral ischemiaalcohol abuse, and stress disorders. Together these findings indicate that only at optimal levels of PTPN5 is synaptic function unimpaired.
phosphatases The Class III PTPs contains three members, CDC25 A, B, and C
Class IV
These are members of the HAD fold and superfamily, and include phosphatases specific to pTyr and pSer/Thr as well as small molecule phosphatases and other enzymes. The subfamily EYA is believed to be pTyr-specific, and has four members in human, EYA1, EYA2, EYA3, and EYA4. This class has a distinct catalytic mechanism from the other three classes.
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 fibronectintype 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 PTPases
Common elements
All PTPases, other than those of the eya family, carry the highly conserved active sitemotif C5R, 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 expressed 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 cells and B cells 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. The expression of PTPN5 is restricted to the brain. Differential expression of PTPN5 is found in many brain regions, with no expression in the cerebellum.
