Protein tyrosine phosphatase receptor-type O truncated (PTPROt) regulates SYK phosphorylation, proximal B-cell-receptor signaling, and cellular proliferation

Linfeng Chen, Przemyslaw Juszczynski, Kunihiko Takeyama, Ricardo C.T. Aguiar, Margaret A. Shipp

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

The strength and duration of B-cell-receptor (BCR) signaling depends upon the balance between protein tyrosine kinase (PTK) activation and protein tyrosine phosphatase (PTP) inhibition. BCR-dependent activation of the SYK PTK initiates downstream signaling events and amplifies the original BCR signal. Although BCR-associated SYK phosphorylation is clearly regulated by PTPs, SYK has not been identified as a direct PTP substrate. Herein, we demonstrate that SYK is a major substrate of a tissue-specific and developmentally regulated PTP, PTP receptor-type O truncated (PTPROt). PTPROt is a member of the PTPRO family (also designated GLEPP, PTP-Ø, PTP-oc, and PTPu2), a group of highly conserved receptor-type PTPs that are thought to function as tumor suppressor genes. The overexpression of PTPROt inhibited BCR-triggered SYK tyrosyl phosphorylation, activation of the associated adaptor proteins SHC and BLNK, and downstream signaling events, including calcium mobilization and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) activation. PTPROt overexpression also inhibited lymphoma cell proliferation and induced apoptosis in the absence of BCR cross-linking, suggesting that the phosphatase modulates tonic BCR signaling.

Original languageEnglish (US)
Pages (from-to)3428-3433
Number of pages6
JournalBlood
Volume108
Issue number10
DOIs
StatePublished - Nov 15 2006
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of 'Protein tyrosine phosphatase receptor-type O truncated (PTPROt) regulates SYK phosphorylation, proximal B-cell-receptor signaling, and cellular proliferation'. Together they form a unique fingerprint.

  • Cite this