Tyrosine phosphatases

Tyrosine phosphatases (protein tyrosine phosphatases; PTPases) belong to a group of enzymes that remove phosphate groups by water addition (hydrolysis) of phosphorylated tyrosine residues on peptides and proteins (e.g. serine, threonine or tyrosine) (protein tyrosine phosphatases). They catalyse dephosphorylation and are thus antagonists of the protein kinases (PTKn). A precisely coordinated interaction between the protein tyrosine kinases and the protein tyrosine phosphatases plays a decisive role in maintaining a phosphorylation balance.

About 30% of all cellular proteins are phosphoproteins.

Protein phosphatases are divided into 4 classes:

• Alkaline phosphatases (mainly found in the intestine)
• Ser/Thr-specific phosphatases (subdivided into type 1 and type 2 with a total of 4 representatives: PP1 (PP1G plays a role in blood sugar regulation); PP2A; PP2B (synonym: calcineurin); PP2C)
• Dual-specific protein phosphatases (DSPs: 3 groups with 16 representatives are distinguished - DSP1-DSP16)
• Tyrosine-specific phosphatases (play a role in blood glucose regulation)
• Receptor-like protein tyrosine phosphatases (RPTs: distinguished 8 classes (R 1 to 8). RTPs are bound to the cell membrane and are composed of an extracellular domain, a transmembrane domain and a cytoplasmic region. Class R1 RPTPs include the CD45 family, which is expressed exclusively in the hematopoietic system).
• Intracellular protein tyrosine phosphatases (distinguished 9 classes (NT1-9). Class NT1 is formed by the protein tyrosine phosphatases PTP1B and TC-PTP. PTP1B is one of the most intensively studied intracellular protein tyrosine phosphatases. Protein tyrosine phosphatase 1B (PTP1B) is encoded by the gene PTPN1, which in humans is located on chromosome 20q13.13. PTB1 regulates the cardiovascular effects of leptin. It controls the JAK/STAT pathway by dephophorilizing JAK2. Furthermore, protein tyrosine phosphatase 1B acts as an antagonist of insulin. Polymorphisms in the PTPN1 gene are associated with diabetes mellitus and obesity.

A further classification of protein tyrosine phosphatases can be made by their cellular localization into:

• Receptor-like PTases (these are composed of an extracellular domain, a transmembrane domain and a cytoplasmic region).
• Non-receptor PT ases (intracellular) PTPases. These include the non-receptor PTPases type 1 and 2 (also known as T-cell PTPases).

Phosphorylation of tyrosine is a common post-translational modification that creates new recognition motifs for protein interactions and cell localization, which further influences protein stability and can regulate enzyme activity. Tyrosine-specific protein phosphatases (PTPase) catalyze the removal of phosphate groups bound to a tyrosine residue. This process of tyrosine phosphorylation is thus essential for the control of the cell cycle, cell growth, differentiation, metabolism, cell-cell communication, cell migration, gene transcription, ion channel activity and immune response. Defective phosphorylations contribute to the development of diseases. Furthermore, many protein phosphatases act as tumour suppressors. They can be mutated or under-expressed in various tumour types.

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