Murine peritoneal macrophages induce a novel 60-kDa protein with structural similarity to a tyrosine kinase p56lck-associated protein in response to oxidative stress.
Using differential screening we have cloned a cDNA encoding a novel oxidative stress protein designated A170 from murine peritoneal macrophages. It has a Zn-finger domain, a PEST domain and several potential phosphorylation sites for kinases. Treatments with oxidative stress agents such as diethyl maleate and paraquat increased a 2.0-kilobase A170 mRNA about twofold in the macrophages after 12 hours in culture. However, H2O2 or glucose/glucose oxidase did not increase the level of the A170 mRNA. Using an A170-specific antibody we have detected in the macrophages a 60-kDa protein that was induced 5 to 10 hours after the addition of the oxidative stress agents. A search of sequence databases revealed that the A170 protein is roughly 90% identical to a human protein that binds to the Src homology 2 domain of the T-cell-specific tyrosine kinase p56lck. These features suggest that the A170 protein plays a significant role in oxidative stress-responsive signal transduction in macrophages.
Ishii
T
T
Department of Biochemistry, University of Tsukuba, Ibaraki, Japan.
Yanagawa
T
T
Kawane
T
T
Yuki
K
K
Seita
J
J
Yoshida
H
H
Bannai
S
S
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000737:chemistry; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D017737:Macrophages, Peritoneal / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D017386:Sequence Homology, Amino Acid; D000071456:Sequestosome-1 Protein; D019061:src-Family Kinases / Q000737:chemistry*
D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; D006360:Heat-Shock Proteins; D000071456:Sequestosome-1 Protein; C101343:Sqstm1 protein, mouse; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases