PTPH1 Dephosphorylatesates and Cooperates with p38y MAPK to Increase Ras Oncogenesis through PDZ-Mediated Interaction

Song Wang Hou, Hui Ying Zhi, Nicole Pohl, Mathew Loesch, Xiao Mei Qi, Rong Shan Li, Zainab Basir, Guan Chen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

Protein phosphatases are believed to coordinate with kinases to execute biological functions, but examples of such integrated activities, however, are still missing, In this report, we have identified protein tyrosine phosphatase Hl (PTPHl) as a specific phosphatase for p38-y mitogen-activated protein kinase (MAPK) and shown their cooperative oncogenic activity through direct binding. p387, a Ras effector known to act independent of its phosphorylation, was first shown to require its unique PDZ-binding motif to increase Ras transformation. Yeast two-hybrid screening and in vitro and in vivo analyses further identified PTPHl as a specific p38-y phosphatase through PDZ-mediated binding. Additional experiments showed that PTPHl itself plays a role in Rasdependent malignant growth in vitro and/or in mice by a mechanism depending on its p38-y-binding activity. Moreover, Ras increases both p38γ and PTPHl protein expression and there is a coupling of increased p38", and PTPHl protein expression in primary colon cancer tissues. These results reveal a coordinative oncogenic activity of a MAPK with its specific phosphatase and suggest that PDZ-mediated p387/γPTPH1 complex may be a novel target for Ras-dependent malignancies.

Original languageEnglish (US)
Pages (from-to)2901-2910
Number of pages10
JournalCancer Research
Volume70
Issue number7
DOIs
StatePublished - Apr 1 2010

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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