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Prostaglandins Leukot Essent Fatty Acids. 2015 Feb;93:3-7. doi: 10.1016/j.plefa.2014.10.004. Epub 2014 Oct 29.

Signaling by retinol and its serum binding protein.

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Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, and Department of Nutrition, Case Western Reserve University School of Medicine, 9500 Euclid Ave., Cleveland, OH 44195, USA. Electronic address:


Vitamin A, retinol, circulates in blood bound to retinol-binding protein (RBP) which, in turn, associates with transthyretin (TTR) to form a retinol-RBP-TTR ternary complex. At some tissues, retinol-bound (holo-) RBP is recognized by a membrane protein termed STRA6, which transports retinol from extracellular RBP into cells and, concomitantly, activates a JAK2/STAT3/5 signaling cascade that culminates in induction of STAT target genes. STRA6-mediated retinol transport and cell signaling are critically inter-dependent, and they both require the presence of cellular retinol-binding protein 1 (CRBP1), an intracellular retinol acceptor, as well as a retinol-metabolizing enzyme such as lecithin:retinol acyltransferase (LRAT). STRA6 thus functions as a "cytokine signaling transporter" which couples vitamin A homeostasis and metabolism to cell signaling, thereby regulating gene transcription. Recent studies provided molecular level insights into the mode of action of this unique protein.


Cytokine receptor; JAK/STAT; Retinol-binding protein; STRA6; Vitamin A

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