PTPN1

What is PTPN1 Protein?

PTPN1, also called PTP1B, is an enzyme from the protein tyrosine phosphatase family. It was discovered through its specific enzymatic functions and amino acid structure. PTP1B removes phosphate groups from tyrosine residues, using a conserved catalytic motif that's crucial for its action. It serves as a key inhibitor of insulin signaling by deactivating phosphotyrosine on the insulin receptor. Additionally, PTP1B affects the epidermal growth factor receptor and JAK2/TYK2 kinases, playing a part in regulating cell growth and how cells react to interferons. This protein is widely found in tissues like lymph nodes and the appendix. There are two forms of this gene, each encoding different versions of the protein.

What is the Function of PTPN1 Protein?

PTPN1, or PTP1B, mainly functions by removing phosphate groups from the amino acid tyrosine on proteins, a process known as dephosphorylation. This action is crucial as it influences several cell signaling pathways. By deactivating parts of these pathways, PTP1B controls various functions like cell growth, metabolism, and how cells respond to hormones like insulin. In terms of insulin, PTP1B acts as a regulator that dampens the signal, playing a big role in managing blood sugar levels. Beyond insulin signaling, PTP1B also interacts with other important cellular proteins like the epidermal growth factor receptor and JAK kinases, impacting how cells grow and divide, and respond to other stimuli. In essence, PTP1B is a key regulator ensuring that cellular signals are fine-tuned for proper physiological responses.

PTPN1 Related Signaling Pathway

PTPN1, also known as PTP1B, is pivotal in several cellular signaling pathways. It plays a vital role by dephosphorylating tyrosine residues on proteins involved in signaling cascades. One of its primary functions is to act as a negative modulator of the insulin signaling pathway, which makes it crucial in controlling how the body manages glucose. By interacting with the insulin receptor, PTP1B ensures that the signaling is not excessively activated. Moreover, PTP1B is involved in regulating other pathways, such as those controlled by the epidermal growth factor receptor (EGFR) and the JAK/STAT pathway, both of which are important for cell growth and immune responses. Because it influences these key processes, PTP1B is an important target for drugs aimed at treating conditions like diabetes and cancer, where these signaling pathways may be dysregulated.

PTPN1 Related Diseases

PTPN1, or PTP1B, is closely linked to several diseases, largely due to its role in regulating key signaling pathways. One of its most noted associations is with diabetes, particularly type 2 diabetes. By negatively regulating insulin signaling, PTP1B contributes to insulin resistance, making it a significant target for diabetes treatment research. Apart from diabetes, PTP1B has been implicated in obesity, as its expression can affect energy expenditure and fat storage. In the realm of cancer, PTP1B's role is twofold; it is involved in both promoting and suppressing tumor growth, depending on the cancer type and context. For instance, PTP1B can encourage cancer progression in breast and prostate cancers while acting differently in other tissues. Its diverse roles in these diseases make it an attractive target for developing drugs that could inhibit its activity to treat or manage these conditions more effectively.

Bioapplications of PTPN1

The protein PTPN1, or PTP1B, finds promising bioapplications mainly due to its influence on major signaling pathways. In diabetes research, PTP1B is a popular target because it negatively regulates insulin signaling, offering pathways for improving insulin sensitivity and managing blood sugar levels. This makes it a potential drug target for developing diabetes therapies. In cancer treatment, PTP1B has a dual role. While it can support tumor growth in certain cancers, inhibiting it might halt cancer progression. Considering this, PTPN1 inhibitors are being explored as potential cancer therapies. Its regulatory effects on metabolic pathways also suggest PTPN1's involvement in obesity-related research, with hopes of developing treatments that can address metabolic syndromes more effectively. Hence, PTPN1 holds significant potential in therapeutic advancements for metabolic and cancer-related diseases.

Case Study 1: Liu R. et al. Int J Mol Sci. 2022

Human protein tyrosine phosphatase 1B (PTP1B) acts as a key player for downregulating crucial phosphorylation pathways like those of insulin and EGFR. It's becoming clear that PTP1B is quite involved in cancer development. Some genetic defects in PTP1B are found in cancers, especially B cell and Hodgkin's lymphomas. In this research, they looked into three PTP1B mutations in a type of lymphoma affecting key enzyme regions: WPD-loop (V184D), P-loop (R221G), and Q-loop (G259V). These mutations resulted in a notable drop in enzyme activity, affected protein stability, and altered how the enzyme's active site works. This highlights the importance of these loops in engaging with substrates and helping the reaction along.

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  Fig1. Purification of the PTP1B proteins in the WT and mutants.
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  Fig2. Thermal shift assay of the PTP1B proteins (5 µM) in the presence of 10 X SYPRO in the WT and mutants.

Case Study 2: Wang Q. et al. Bioengineered. 2021

Research has shown that protein tyrosine phosphatase 1B (PTP1B) pushes tumor growth in cancers like breast, colon, and prostate. Surprisingly, it acts as a tumor suppressor in esophageal cancer and lymphoma, making it a complex player in cancer dynamics. While its role in malignant melanoma (MM) wasn't clear, our study explored it further. We checked PTP1B levels in normal and melanoma tissues and found higher expression in melanoma, which linked to worse patient outcomes. Lab tests showed that blocking PTP1B reduces, while boosting it increases, melanoma cell movement and invasion. PTP1B seems to aid melanoma spread by interacting with Src, a pivotal protein, helping its activation by dephosphorylating Src at a specific site. These findings highlight PTP1B's potential as a target for treatments against melanoma.

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  Fig3. Phosphorylation levels of proteins in A2058 cells with knockdown of PTP1B were detected in the Human Phospho-Kinase Array.
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  Fig4. The phosphorylation level of Src Tyr530 was detected in cells with knockdown or overexpression of PTP1B.

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  Fig1. Main physiological functions and signaling pathways modulated by PTP1B. (Andrea Coronell-Tovar, 2024)
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  Fig2. Overview of EGFR, E-Cadherin and PTP1B interactions, and their roles in the maintenance of AJ and intracellular signaling. (Tessa Arnaud, 2023)

PTPN1 has several biochemical functions, for example, enzyme binding,ephrin receptor binding,insulin receptor binding. Some of the functions are cooperated with other proteins, some of the functions could acted by PTPN1 itself. We selected most functions PTPN1 had, and list some proteins which have the same functions with PTPN1. You can find most of the proteins on our site.

Function	Related Protein
insulin receptor binding	INSL3,DOK2,PIK3R1,ENPP1,DOK3,IGF1R,PTPN11,DOK7,FRS3,PDPK1
enzyme binding	CD4,HIST1H2AI,WWOX,PRKCH,TSPAN33,RPA3,HSPA5,ATG3,PLSCR1,VAPB
protein tyrosine phosphatase activity	PTPN2A,CDC25D,CDC14B,DUSP3,PTPRZ1,PTPRU,EYA3,MTMR8,PTPN4A,TIMM50
receptor tyrosine kinase binding	ANGPT2A,GAS6,PIK3R2,PCNA,ANGPT2,FLT3LG,ANXA5,FIZ1,PTPN11,TOB1
protein phosphatase 2A binding	STRN4,IGBP1,PPP2R4,PPP2R2A,SMG7,FOXO1,SPHK1,ARPP19,TRP53,EIF4EBP1
protein kinase binding	EEF1A1,MAVS,CDKN2B,TBC1D14,MEF2A,CALM2,GYS1,ATP1A1,CDK5,CNPPD1
protein binding	ESRRA,STK4,GTF2E1,CEBPB,NUS1,MSN,TRMT61B,RND2,MTERFD2,MTMR4
zinc ion binding	PDZRN4,ZMIZ2,UNK,PAM,CHD4,BTR30,TNP2,ZRANB2,ERI2,FTR72
poly(A) RNA binding	HSD17B10,ALG13,RBM25,C11orf68,HDLBP,XRCC6,RPL32,PDCD11,SRP54,EXOSC6

PTPN1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with PTPN1 here. Most of them are supplied by our site. Hope this information will be useful for your research of PTPN1.

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