Redox regulation of a protein tyrosine kinase in the endoplasmic reticulum

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EPR Monitored Redox Titration of the Cofactors of Saccharomyces cerevisiae Nar1
06:01

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A R Bauskin1, I Alkalay, Y Ben-Neriah

  • 1Lautenberg Center for General and Tumor Immunology, Hebrew University, Hadassah Medical School, Jerusalem, Israel.

Cell
|August 23, 1991
PubMed

Insights

The mouse Ltk protein tyrosine kinase is unusually located in the endoplasmic reticulum (ER). Its activity is regulated by cellular redox potential, a novel mechanism for protein tyrosine kinases.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Protein tyrosine kinases (PTKs) play crucial roles in cellular signaling.
  • The Ltk transmembrane protein tyrosine kinase's function and localization are not fully understood.
  • Receptor tyrosine kinases are typically localized to the plasma membrane.

Purpose of the Study:

  • To determine the subcellular localization of the mouse Ltk protein tyrosine kinase.
  • To investigate the regulatory mechanisms of Ltk activity.

Main Methods:

  • Indirect immunofluorescence and immunogold staining in transfected COS cells and lymphocytes.
  • Endoglycosidase analysis of Ltk in COS transfectants and lymphocytes.

Main Results:

  • Ltk was found to be unusually localized to the endoplasmic reticulum (ER).
  • Ltk activity is enhanced by alkylating and thiol-oxidizing agents, suggesting ligand-independent function.
  • Active Ltk exists as disulfide-linked multimers, indicating redox regulation.

Conclusions:

  • Ltk's catalytic activity in the ER may be regulated by cellular redox potential, a novel mechanism for PTKs.
  • This redox-sensitive regulation in the ER might be a shared feature with some receptor kinases.

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