Question

The protein phosphatase PTP1B is a negative regulator of the insulin production pathway. Mutation of PTP1B results in uncontrolled insulin production. Describe the role protein phosphatases play in cell signaling and discuss how their role relates to the overproduction of insulin in cells with mutant PTP1B.

Answer 1

Ans-Protein phosphorylation is an important cellular regulatory mechanism as many enzymes and receptors are activated/deactivated by phosphorylation and dephosphorylation events, by means of kinases and phosphatases. In particular, the protein kinases are responsible for cellular transduction signaling and their hyperactivity, malfunction or overexpression can be found in several diseases, mostly tumors.The mechanism of phosphorylation regulation consists of kinases, phosphatases and their substrates phospho-binding proteins. For example, phosphorylation is activated by stimuli such as epigenetic modifications, cytogenetic alterations, genetic mutations or the tumor micro-environment. Consequently, the protein receives a phosphate group by adenosine triphosphate (ATP) hydrolysis and due to enzymatic activity of kinase. This is the mechanism for the basis of post-translational modification (PTM) formation. In addition, phosphorylation is a reversible process due to activity of phosphatase. Phosphorylation and dephosphorylation are a molecular switch and, in particular, a PTM can cause oncogenic pathway activation by a phospho-binding protein that bind to the phosphate group of a phosphoprotein.​​​​​​

• the cellular role of the protein-tyrosine phosphatase PTP1B it serves as a key negative regulator of the tyrosine phosphorylation cascade integral to the insulin signaling pathway.
• Genetically-modified mice that lack PTP1B protein expression and animals treated with a specific PTP1B antisense oligonucleotide have provided crucial "proof-of-concept" data to show that eradicating or reducing PTP1B enhances insulin signaling and glucose tolerance.
• PTP1B inhibition also reduces adipose tissue storage of triglyceride under conditions of over-nutrition and was not associated with any obvious toxicity.
• Tyrosine-protein phosphatase non-receptor type 1 also known as protein-tyrosine phosphatase 1B (PTP1B) is an enzyme that is the founding member of the protein tyrosine phosphatase (PTP) family. In humans it is encoded by the PTPN1 gene.