Abstract:
The role of non-receptor type Protein Tyrosine Phosphatase (PTPases) in controlling pathways related to diabetes and Hepatocellular Carcinoma (HCC) is significant. The insulin signal transduction pathway is regulated by the steady-state phosphorylation of tyrosyl residues of the insulin receptor and post-receptor substrates. PTPase has been shown to have a physiological role in the regulation of reversible tyrosine phosphorylation. There are several non-receptor type PTPases. PTPase containing the SH-2 domain (SHP-2) and the non-receptor type PTPase (PTP1B; encoded by the PTPN1 gene) are involved in negative regulation of the insulin signaling pathway, thereby indicating that the pathway can be made more efficient by the reduction in the activity of specific PTPases. Reduction in insulin resistance may be achieved by drugs targeting these specific enzymes. The modifications in the receptor and post-receptor events of insulin signal transduction give rise to insulin resistance, and a link between insulin-resistant states and HCC has been established. The cancer cells thrive on higher levels of energy and their growth gets encouraged since insulin-resistant states lead to greater glucose levels. Cancer, hyperglycemia, and hypoglycemia are highly linked through various pathways hence, clarifying the molecular mechanisms through which non-receptor type PTPase regulates the insulin signal transduction is necessary to find an effective target for cancer. Targeting the pathways related to PTPases; both receptor and non-receptor types, may lead to an effective candidate to fight against diabetes and HCC.
摘要:
非受体型蛋白酪氨酸磷酸酶(PTPases)在控制与糖尿病和肝细胞癌(HCC)相关的途径中的作用是重要的。胰岛素信号转导途径受胰岛素受体和后受体底物的酪氨酰残基的稳态磷酸化调节。PTPase已显示在可逆酪氨酸磷酸化的调节中具有生理作用。有几种非受体型PTPase。含有SH-2结构域(SHP-2)和非受体型PTPase(PTP1B;由PTPN1基因编码)的PTPase参与胰岛素信号通路的负调节,从而表明通过降低特异性PTPase的活性可以使途径更有效。胰岛素抵抗的降低可以通过靶向这些特定酶的药物来实现。胰岛素信号转导的受体和受体后事件的修饰引起胰岛素抵抗,胰岛素抵抗状态和肝癌之间的联系已经建立。癌细胞在更高水平的能量下茁壮成长,并且由于胰岛素抵抗状态导致更高的葡萄糖水平,它们的生长得到了鼓励。癌症,高血糖症,和低血糖是通过各种途径高度关联的,阐明非受体型PTPase调节胰岛素信号转导的分子机制是寻找癌症有效靶点的必要条件。靶向与PTPases相关的途径;受体和非受体类型,可能导致有效的候选人对抗糖尿病和肝癌。