Identification of phosphocaveolin-1 as a novel protein tyrosine phosphatase 1B substrate

Hyangkyu Lee, Laiping Xie, Yong Luo, Seung Yub Lee, David S. Lawrence, Xiao Bo Wang, Federica Sotgia, Michael P. Lisanti, Zhong Yin Zhang

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Protein tyrosine phosphatase 1B (PTP1B) is implicated in a number of signaling pathways including those mediated by insulin, epidermal growth factor (EGF), and the Src family kinases. The scaffolding protein caveolin-1 is also a participant in these pathways and is specifically phosphorylated on tyrosine 14, when these pathways are activated. Here, we provide evidence that PTP1B can efficiently catalyze the removal of the phosphoryl group from phosphocaveolin-1. Overexpression of PTP1B decreases tyrosine 14 phosphorylation in caveolin-1, while expression of the substrate-trapping mutant PTP1B/D181A causes the accumulation of phosphocaveolin-1 and prevents its dephosphorylation by endogenous PTPs. We further demonstrate that PTP1B physically associates with caveolin-1. Finally, we show that inhibition of PTP1B activity with a potent and specific small molecule PTP1B inhibitor blocks the PTP1B-catalyzed caveolin-1 dephosphorylation both in vitro and in vivo. Taken together, the results strongly suggest that caveolin-1 is a specific substrate for PTP1B. Identification of caveolin-1 as a PTP1B substrate represents an important new step in further understanding the signaling pathways regulated by PTP1B.

Original languageEnglish
Pages (from-to)234-240
Number of pages7
JournalBiochemistry
Volume45
Issue number1
DOIs
Publication statusPublished - 2006 Jan 10

All Science Journal Classification (ASJC) codes

  • Biochemistry

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    Lee, H., Xie, L., Luo, Y., Lee, S. Y., Lawrence, D. S., Wang, X. B., Sotgia, F., Lisanti, M. P., & Zhang, Z. Y. (2006). Identification of phosphocaveolin-1 as a novel protein tyrosine phosphatase 1B substrate. Biochemistry, 45(1), 234-240. https://doi.org/10.1021/bi051560j