Langlet Christelle, Nachtergael Ingrid, Robberecht Patrick, Langer Ingrid
Laboratoire de Chimie Biologique et de la Nutrition, School of Medicine, Université Libre de Bruxelles, 808 Route de Lennik-CP611, B-1070 Bruxelles, Belgium.
Peptides. 2006 Jul;27(7):1865-70. doi: 10.1016/j.peptides.2006.01.010. Epub 2006 Mar 22.
The hVPAC1 receptor is rapidly phosphorylated and internalized by agonists but not re-expressed at the membrane after washing. Mutation of Ser/Thr residues in the C-terminus reduced phosphorylation but not internalization that was abolished only when all the phosphorylatable residues were mutated. Substitution of Thr429 by Glu mimicking a phosphothreonin led to a mutant with unchanged binding properties, decreased coupling to adenylate cyclase consisting in a reduced VIP potency, increased basal and VIP stimulated phosphorylation, preserved internalization followed by a rapid receptor re-expression. These are the expected characteristics of a constitutively desensitized receptor, putting forward the role of Thr429 phosphorylation in that process.
hVPAC1受体可被激动剂迅速磷酸化并内化，但洗涤后不会在细胞膜上重新表达。C末端的丝氨酸/苏氨酸残基发生突变会降低磷酸化，但不会影响内化，只有当所有可磷酸化残基都发生突变时，内化才会被消除。将苏氨酸429替换为模拟磷酸苏氨酸的谷氨酸会产生一个突变体，其结合特性不变，与腺苷酸环化酶的偶联减少，表现为VIP效力降低，基础磷酸化和VIP刺激的磷酸化增加，内化得以保留，随后受体快速重新表达。这些是组成型脱敏受体的预期特征，表明苏氨酸429磷酸化在该过程中的作用。
