Synthesis of p36 and p35 is increased when U-937 cells differentiate in culture but expression is not inducible by glucocorticoids.
p36 and p35 are distinct but related proteins that share many structural and biochemical features which were first identified as major substrates for protein-tyrosine kinases. Subsequently, both proteins have been shown to be Ca2+-, phospholipid-, and F-actin-binding proteins that underlie the plasma membrane and are associated with the cortical cytoskeleton. Recent reports have claimed that these proteins function as lipocortins, i.e., phospholipase A2 inhibitors that mediate the anti-inflammatory action of glucocorticoids. To investigate this possibility and to learn more about the functions of p36 and p35, we used human-specific anti-p36 and anti-p35 monoclonal antibodies to determine whether the expression or secretion of either protein was inducible by dexamethasone in the human U-937 myeloid cell line and in other human cell types. Additionally, we examined the levels of mRNA for both proteins. No effect of dexamethasone was observed on p36 or p35 expression at either the mRNA or protein level, nor were these proteins secreted under any of the culture conditions investigated. However, it was observed that in these cells the rate of synthesis and accumulation of both proteins was increased when the U-937 cells were induced to differentiate in culture to adherent macrophagelike cells. This offers a model system with which to study the control of p36 and p35 expression.
Isacke
C M
CM
Molecular Biology and Virology Laboratory, Salk Institute, San Diego, California 92138.
Lindberg
R A
RA
Hunter
T
T
D000818:Animals; D017302:Annexins; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D015152:Blotting, Northern; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007951:Leukemia, Myeloid / Q000378:metabolism; D051379:Mice; D014176:Protein Biosynthesis / Q000187:drug effects; D012313:RNA / Q000032:analysis; D014407:Tumor Cells, Cultured
D017302:Annexins; D000911:Antibodies, Monoclonal; D002135:Calcium-Binding Proteins; D005938:Glucocorticoids; D012313:RNA; D003907:Dexamethasone