Analysis of PTP1B sumoylation

Saha, Sayanti; Chernoff, Jonathan

doi:10.1016/j.ymeth.2013.09.012

Cited by 6 publications

(2 citation statements)

References 23 publications

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“…Several studies suggested that these sites may be modified in response to osmotic stress, and do not impair PTP1B activity [22,23]. Similarly, sumoylation was reported at Lys73, Lys335, Lys347 and Lys389 [10]. Although crystal structures of PTP1B do not include residues beyond 321, these sumoylation sites are located close to PTP1B catalytic site, suggesting that these PTMs may alter the conformation of PTP1B through steric hindrances, thereby reducing interactions with PTP1B substrates and resulting in reduced enzymatic activity [4,24].…”

Section: Regulatory Domainmentioning

confidence: 98%

“…As stated above, given its key functions in several signaling cascades, PTP1B activity is regulated by several mechanisms that may work in tandem to modulate the enzyme's functions. Especially, reversible and irreversible post-translational modifications (PTMs) such as phosphorylation, oxidation, sumoylation, and proteolysis, were put forward as essential for regulating PTP1B activity [4,[7][8][9][10]. Further mechanistic implications of PTP1B and its modulation can be found in the study by Yip et al [4].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Human Protein Tyrosine Phosphatase 1B (PTP1B): From Structure to Clinical Inhibitor Perspectives

Liu

Mathieu²,

Berthelet

et al. 2022

IJMS

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Phosphorylation is an essential process in biological events and is considered critical for biological functions. In tissues, protein phosphorylation mainly occurs on tyrosine (Tyr), serine (Ser) and threonine (Thr) residues. The balance between phosphorylation and dephosphorylation is under the control of two super enzyme families, protein kinases (PKs) and protein phosphatases (PPs), respectively. Although there are many selective and effective drugs targeting phosphokinases, developing drugs targeting phosphatases is challenging. PTP1B, one of the most central protein tyrosine phosphatases (PTPs), is a key player in several human diseases and disorders, such as diabetes, obesity, and hematopoietic malignancies, through modulation of different signaling pathways. However, due to high conservation among PTPs, most PTP1B inhibitors lack specificity, raising the need to develop new strategies targeting this enzyme. In this mini-review, we summarize three classes of PTP1B inhibitors with different mechanisms: (1) targeting multiple aryl-phosphorylation sites including the catalytic site of PTP1B; (2) targeting allosteric sites of PTP1B; (3) targeting specific mRNA sequence of PTP1B. All three types of PTP1B inhibitors present good specificity over other PTPs and are promising for the development of efficient small molecules targeting this enzyme.

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