Pulling strings below the surface: Hormone receptor signaling through inhibition of protein tyrosine phosphatases

X. Espanel, S. Wälchli, R. P. Gobert, M. E. Alama, M. L. Curchod, N. Gullu-Isler, R. Hooft van Huijsduijnen

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Hormones, cytokines, and related proteins (such as soluble hormone receptors) play an important role as therapeutic agents. Most hormone receptors signal through a mechanism that involves phosphorylation of the receptor's tyrosine residues. At any given moment, the receptor's phosphorylation state depends on the balance of kinase and phosphatase activities. Recent findings point to the exciting possibility that receptor signaling can be regulated by inhibition of protein tyrosine phosphatases (PTPs) that specifically hydrolyze receptor tyrosine-phosphates, or their immediate downstream effectors. This strategy has now been firmly validated for the insulin receptor and PTP1B; inhibiting PTP1B activity results in stimulation of the insulin receptor and signaling, even in the absence of insulin. This and similar findings suggest that PTP inhibitors have potential as hormone mimetics. In the present review, we outline this new paradigm for therapeutic regulation of the insulin receptor and discuss evidence that hints at other specific receptor-PTP pairs.

Original languageEnglish (US)
Pages (from-to)19-28
Number of pages10
JournalEndocrine
Volume15
Issue number1
StatePublished - Jan 1 2001

Fingerprint

Protein Tyrosine Phosphatases
Insulin Receptor
Hormones
Phosphorylation
Phosphoric Monoester Hydrolases
Phosphotransferases
Phosphates
Insulin
Cytokines
Therapeutics
Proteins
tyrosine receptor

Keywords

  • Cytokines
  • Insulin
  • PTP1B
  • Protein tyrosine kinase
  • Protein tyrosine phosphatase

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Espanel, X., Wälchli, S., Gobert, R. P., Alama, M. E., Curchod, M. L., Gullu-Isler, N., & Hooft van Huijsduijnen, R. (2001). Pulling strings below the surface: Hormone receptor signaling through inhibition of protein tyrosine phosphatases. Endocrine, 15(1), 19-28.

Pulling strings below the surface : Hormone receptor signaling through inhibition of protein tyrosine phosphatases. / Espanel, X.; Wälchli, S.; Gobert, R. P.; Alama, M. E.; Curchod, M. L.; Gullu-Isler, N.; Hooft van Huijsduijnen, R.

In: Endocrine, Vol. 15, No. 1, 01.01.2001, p. 19-28.

Research output: Contribution to journalArticle

Espanel, X, Wälchli, S, Gobert, RP, Alama, ME, Curchod, ML, Gullu-Isler, N & Hooft van Huijsduijnen, R 2001, 'Pulling strings below the surface: Hormone receptor signaling through inhibition of protein tyrosine phosphatases', Endocrine, vol. 15, no. 1, pp. 19-28.
Espanel X, Wälchli S, Gobert RP, Alama ME, Curchod ML, Gullu-Isler N et al. Pulling strings below the surface: Hormone receptor signaling through inhibition of protein tyrosine phosphatases. Endocrine. 2001 Jan 1;15(1):19-28.
Espanel, X. ; Wälchli, S. ; Gobert, R. P. ; Alama, M. E. ; Curchod, M. L. ; Gullu-Isler, N. ; Hooft van Huijsduijnen, R. / Pulling strings below the surface : Hormone receptor signaling through inhibition of protein tyrosine phosphatases. In: Endocrine. 2001 ; Vol. 15, No. 1. pp. 19-28.
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