Inhibition of cell migration by autophosphorylated mammalian sterile 20-like kinase 3 (MST3) involves paxillin and protein-tyrosine phosphatase-PEST

Te Jung Lu, Wen Yang Lai, Chi Ying F Huang, Wan Jung Hsieh, Jau Song Yu, Ya Ju Hsieh, Wen Tsan Chang, Tzeng Horng Leu, Wen Chang Chang, Woei Jer Chuang, Ming Jer Tang, Tzong Yueh Chen, Te Ling Lu, Ming Derg Lai

Research output: Contribution to journalArticle

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Abstract

MST3 is a member of the sterile-20 protein kinase family with a unique preference for manganese ion as a cofactor in vitro; however, its biological function is largely unknown. Suppression of endogenous MST3 by small interference RNA enhanced cellular migration in MCF-7 cells with reduced expression of E-cadherin at the edge of migrating cells. The alteration of cellular migration and protruding can be rescued by RNA interference-resistant MST3. The expression of surface integrin and Golgi apparatus was not altered, but phosphorylation on tyrosine 118 and tyrosine 31 of paxillin was attenuated by MST3 small interfering RNA (siRNA). Threonine 178 was determined to be one of the two main autophosphorylation sites of MST3 in vitro. Mutant T178A MST3, containing alanine instead of threonine at codon 178, lost autophosphorylation and kinase activities. Overexpression of wild type MST3, but not the T178A mutant MST3, inhibited migration and spreading in Madin-Darby canine kidney cells. MST3 could phosphorylate the protein-tyrosine phosphatase (PTP)-PEST and inhibit the tyrosine phosphatase activity of PTP-PEST. We conclude that MST3 inhibits cell migration in a fashion dependent on autophosphorylation and may regulate paxillin phosphorylation through tyrosine phosphatase PTP-PEST.

Original languageEnglish
Pages (from-to)38405-38417
Number of pages13
JournalJournal of Biological Chemistry
Volume281
Issue number50
DOIs
Publication statusPublished - Dec 15 2006
Externally publishedYes

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Cell Migration Inhibition
Paxillin
Protein Tyrosine Phosphatases
Tyrosine
Phosphorylation
Phosphotransferases
Cells
Threonine
RNA Interference
RNA
Phosphatases
Cadherins
Manganese
Phosphoric Monoester Hydrolases
Integrins
Alanine
Protein Kinases
Small Interfering RNA
Madin Darby Canine Kidney Cells
MCF-7 Cells

ASJC Scopus subject areas

  • Biochemistry

Cite this

Inhibition of cell migration by autophosphorylated mammalian sterile 20-like kinase 3 (MST3) involves paxillin and protein-tyrosine phosphatase-PEST. / Lu, Te Jung; Lai, Wen Yang; Huang, Chi Ying F; Hsieh, Wan Jung; Yu, Jau Song; Hsieh, Ya Ju; Chang, Wen Tsan; Leu, Tzeng Horng; Chang, Wen Chang; Chuang, Woei Jer; Tang, Ming Jer; Chen, Tzong Yueh; Lu, Te Ling; Lai, Ming Derg.

In: Journal of Biological Chemistry, Vol. 281, No. 50, 15.12.2006, p. 38405-38417.

Research output: Contribution to journalArticle

Lu, TJ, Lai, WY, Huang, CYF, Hsieh, WJ, Yu, JS, Hsieh, YJ, Chang, WT, Leu, TH, Chang, WC, Chuang, WJ, Tang, MJ, Chen, TY, Lu, TL & Lai, MD 2006, 'Inhibition of cell migration by autophosphorylated mammalian sterile 20-like kinase 3 (MST3) involves paxillin and protein-tyrosine phosphatase-PEST', Journal of Biological Chemistry, vol. 281, no. 50, pp. 38405-38417. https://doi.org/10.1074/jbc.M605035200
Lu, Te Jung ; Lai, Wen Yang ; Huang, Chi Ying F ; Hsieh, Wan Jung ; Yu, Jau Song ; Hsieh, Ya Ju ; Chang, Wen Tsan ; Leu, Tzeng Horng ; Chang, Wen Chang ; Chuang, Woei Jer ; Tang, Ming Jer ; Chen, Tzong Yueh ; Lu, Te Ling ; Lai, Ming Derg. / Inhibition of cell migration by autophosphorylated mammalian sterile 20-like kinase 3 (MST3) involves paxillin and protein-tyrosine phosphatase-PEST. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 50. pp. 38405-38417.
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AU - Hsieh, Wan Jung

AU - Yu, Jau Song

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AU - Chuang, Woei Jer

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