title: All-trans-retinoic acid and Erk1/2 signaling synergistically regulate the expression of CD300B in human monocytic cells.
abstract: The regulation of the cell-surface receptors that constitute the gene cluster, CD300, also known as the Myeloid Activating/Inhibitory Receptor (MAIR) family, is poorly understood. In the present study, we tested the hypothesis that all-trans-RA (RA), a bioactive form of vitamin A long recognized for its role in regulation of immune cell activities, may be a potent regulator of the expression of human CD300B. In monocytic THP-1 cells, RA (20nM) alone significantly increased CD300B mRNA within 2h and up to 20-fold after 24h; however, CD300B protein determined by flow cytometry and confocal microscopy showed little change. A search for coactivating molecules revealed that phorbol myristyl acetate (PMA), a mimetic of diacylglycerol, alone increased CD300B mRNA by less than 5-fold; however, the combination of at-RA and PMA increased CD300B mRNA nearly 60-fold. Moreover, CD300B protein was increased. CD300B molecules were mainly located on the plasma membrane and in the endosomal compartment, sharing a distribution/recycling pattern similar to transferrin receptor CD71. The induction of CD300B mRNA by PMA required signaling through the MEK/ERK branch of the MAP kinase pathway, as PD98059, a MEK1/2 inhibitor, abrogated this response, while SB203580, an inhibitor of the p38 pathway, had no effect. Our data suggest a model in which RA alone induces a CD300B mRNA response in which transcripts accumulate but remain untranslated and therefore "sterile," whereas RA combined with signals from the ERK1/2 pathway results in both increased CD300B transcription and protein expression on the cell surface and in endocytic vesicles.
authors: Department of Nutritional Sciences, Pennsylvania State University, University Park, PA 16802, USA.
authors: Yong
authors: Y
authors: Wu
authors: Qiuyan
authors: Q
authors: Chen
authors: Tongkun
authors: T
authors: Pai
authors: A Catharine
authors: AC
authors: Ross
mesh_terms: D045744:Cell Line, Tumor; D005419:Flavonoids / Q000494:pharmacology; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D018613:Microscopy, Confocal; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: C519445:CD300LB protein, human; D005419:Flavonoids; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D014212:Tretinoin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one