Roles of the α1B-Adrenergic Receptor Phosphorylation Domains in Signaling and Internalization

被引:1
|
作者
Hernandez-Espinosa, David A. [1 ]
Alcantara-Hernandez, Rocio [1 ]
Solis, K. Helivier [1 ]
Garcia-Sainz, J. Adolfo [1 ]
机构
[1] Univ Nacl Autonoma Mexico, Dept Biol Celular & Desarrollo, Inst Fisiol Celular, Ciudad Univ, Mexico City 04510, Mexico
关键词
alpha(1B)-adrenergic receptor; receptor phosphorylation; receptor desensitization; receptor internalization; phosphorylation sites; PROTEIN-COUPLED RECEPTOR; DESENSITIZATION; SUBTYPES;
D O I
10.3390/ijms242316963
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The function of the alpha(1B)-adrenergic receptor phosphorylation sites previously detected by mass spectrometry was evaluated by employing mutants, substituting them with non-phosphorylatable amino acids. Substitution of the intracellular loop 3 (IL3) sites did not alter baseline or stimulated receptor phosphorylation, whereas substitution of phosphorylation sites in the carboxyl terminus (Ctail) or both domains (IL3/Ctail) markedly decreased receptor phosphorylation. Cells expressing the IL3 or Ctail receptor mutants exhibited a noradrenaline-induced calcium-maximal response similar to those expressing the wild-type receptor, and a shift to the left in the concentration-response curve to noradrenaline was also noticed. Cells expressing the IL3/Ctail mutant exhibited higher apparent potency and increased maximal response to noradrenaline than those expressing the wild-type receptor. Phorbol ester-induced desensitization of the calcium response to noradrenaline was reduced in cells expressing the IL3 mutant and abolished in cells in which the Ctail or the IL3/Ctail were modified. In contrast, desensitization in response to preincubation with noradrenaline was unaffected in cells expressing the distinct receptor mutants. Noradrenaline-induced ERK phosphorylation was surprisingly increased in cells expressing IL3-modified receptors but not in those expressing receptors with the Ctail or IL3/Ctail substitutions. Our data indicate that phosphorylation sites in the IL3 and Ctail domains mediate and regulate alpha(1B)-adrenergic receptor function. Phorbol ester-induced desensitization seems to be closely associated with receptor phosphorylation, whereas noradrenaline-induced desensitization likely involves other elements.
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页数:15
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