Redox regulation of a protein tyrosine kinase in the endoplasmic reticulum

Asne R. Bauskin*, Irit Alkalay, Yinon Ben-Neriah

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

248 Scopus citations

Abstract

The subcellular localization of the mouse Ltk transmembrane protein tyrosine kinase was studied in transfected COS cells, a mature B lymphocyte line, and a low expressing transfected lymphocyte clone. Indirect immunofluorescence and immunogold staining of COS transfectants and endoglycosidase analysis of both COS transfectants and lymphocytes indicate the unusual localization of Ltk to the endoplasmic reticulum (ER). Ltk resembles a receptor tyrosine kinase; it has a short, glycosylated, and cysteine-rich N-terminal domain. Yet, it appears to function in a ligand-independent mechanism: its in vivo catalytic activity is markedly enhanced by alkylating and thioloxidizing agents, and the active fraction of the protein occurs as disulfide-linked multimers. The catalytic activity of Ltk in the ER may be regulated via changes in the cellular redox potential, a novel mechanism for regulating protein tyrosine kinases. The ability to respond to redox changes in the cell may, however, be shared with certain receptor kinases during their passage through the ER.

Original languageAmerican English
Pages (from-to)685-696
Number of pages12
JournalCell
Volume66
Issue number4
DOIs
StatePublished - 23 Aug 1991

Bibliographical note

Funding Information:
We would like to thank Drs. Andre Bernards, Derek LeRoith, Daniel Louvard, David Stern, and Yehiel Zick for providing antibodies; Dr. Andre Bernards for the 22D8 Ltk expression vector; Dr. Yosef Yarden for the neu expression vector and antibodies; Dr. W. J. Rutter for the insulin receptor cDNA, Miriam Golembo for her help in the initial experiments; Rina Timberg and Dr. Joseph Orly for their help in the electron microscopy; Dr. Michal Baniyash for her advice on the two-dimensional gel electrophoresis; Drs. Yoav Citri and Yosef Yarden for critical reading of the manuscript; and Marcella Wachtel for her assistance in typing. This work was supported by grants from the Israel Cancer Research Fund, The Wolfson Research Awards administered by the Israel Academy of Sciences, and the Society of the Research Associates of the Lautenberg Center.

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