Redox regulation of a protein tyrosine kinase in the endoplasmic reticulum.
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 thiol-oxidizing 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.
Bauskin
A R
AR
Lautenberg Center for General and Tumor Immunology, Hebrew University, Hadassah Medical School, Jerusalem, Israel.
Alkalay
I
I
Ben-Neriah
Y
Y
D000818:Animals; D002451:Cell Compartmentation; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D003958:Diamide / Q000737:chemistry; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D004789:Enzyme Activation; D005455:Fluorescent Antibody Technique; D006031:Glycosylation; D007150:Immunohistochemistry; D007425:Intracellular Membranes / Q000378:metabolism; D007460:Iodoacetamide / Q000737:chemistry; D008562:Membrane Glycoproteins / Q000378:metabolism; D010084:Oxidation-Reduction; D010750:Phosphoproteins / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases; D011956:Receptors, Cell Surface / Q000378:metabolism
D008562:Membrane Glycoproteins; D010750:Phosphoproteins; D011956:Receptors, Cell Surface; D003958:Diamide; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D007460:Iodoacetamide