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Two threonine residues and two serine residues in the second and third intracellular loops are both involved in histamine H 1 receptor downregulation
Author(s) -
Horio Shuhei,
Kato Toshiyuki,
Ogawa Maki,
Fujimoto Katsumi,
Fukui Hiroyuki
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.07.072
Subject(s) - downregulation and upregulation , serine , alanine , threonine , chemistry , receptor , phosphorylation , agonist , mutant , residue (chemistry) , biochemistry , microbiology and biotechnology , biology , amino acid , gene
Human histamine H 1 receptor (H 1 R) contains five possible phosphorylation residues (Thr 140 , Thr 142 , Ser 396 , Ser 398 and Thr 478 ) 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 H 1 Rs in which single or multiple residues were substituted with alanine. The results suggested that two groups, i.e., residues Thr 140 and Thr 142 , and residues Ser 396 and Ser 398 , independently contributed to H 1 R downregulation. Thr 140 and Ser 398 mainly contributed to downregulation, and Thr 142 or Ser 396 had a slight inhibitory effect on Thr 140 ‐ or Ser 398 ‐mediated process, respectively.