Horio Shuhei, Kato Toshiyuki, Ogawa Maki, Fujimoto Katsumi, Fukui Hiroyuki
Department of Molecular Pharmacology, Division of Pharmaceutical Sciences, Graduate School of Health and Bioscience, the University of Tokushima, 1-78-1 Shomachi, Tokushima 770-8505, Japan.
FEBS Lett. 2004 Aug 27;573(1-3):226-30. doi: 10.1016/j.febslet.2004.07.072.
Human histamine H1 receptor (H1R) contains five possible phosphorylation residues (Thr140, Thr142, Ser396, Ser398 and Thr478) and the substitution of all these five residues to alanine completely impairs agonist-induced receptor downregulation. In the present study, to determine which residue(s) are responsible for receptor downregulation, we used mutant H1Rs in which single or multiple residues were substituted with alanine. The results suggested that two groups, i.e., residues Thr140 and Thr142, and residues Ser396 and Ser398, independently contributed to H1R downregulation. Thr140 and Ser398 mainly contributed to downregulation, and Thr142 or Ser396 had a slight inhibitory effect on Thr140- or Ser398-mediated process, respectively.
