Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.12.2 (MEK)
 18,161 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:All-trans-retinoic acid and Erk1/2 signaling synergistically regulate the expression of CD300B in human monocytic cells. 2145 Feb 79