Bombyx Adipokinetic Hormone Receptor Activates Extracellular Signal-Regulated Kinase 1 and 2 via G Protein-Dependent PKA and PKC but β-Arrestin-Independent Pathways

作者：Huang, Haishan; He, Xiaobai; Deng, Xiaoyan; Li, Guo; Ying, Guoyuan; Sun, Yi; Shi, Liangen; Benovic, Jeffrey L.; Zhou, Naiming^*

来源：Biochemistry, 2010, 49(51): 10862-10872.

DOI：10.1021/bi1014425

• GROWTH-FACTOR RECEPTOR
• CORPORA CARDIACA
• FAT-BODY
• COUPLED RECEPTORS
• SENSITIVE LIPASE
• MANDUCA-SEXTA
• GLYCOGEN-PHOSPHORYLASE
• STIMULATED LIPOLYSIS
• LOCUSTA-MIGRATORIA
• ERK1/2 ACTIVATION

Neuropeptides of the adipokinetic hormone (AKH) family are among the best studied hormone peptides. They play important roles in insect hemolymph sugar homeostasis, larval lipolysis, and storage-fat mobilization. Mechanistic investigations have shown that, upon AKH stimulation, adipokinetic hormone receptor (AKHR) couples to a Gs protein and enhances adenylate cyclase activity, leading to intracellular cAMP accumulation. However, the underlying molecular mechanism by which this signaling pathway connects to extracellular signal-regulated kinase 1/2 (ERK1/2) remains to be elucidated. Using HEK293 cells stably or transiently expressing AKHR, we demonstrated that activation of AKHR elicited transient phosphorylation of ERK1/2. Our investigation indicated that AKHR-mediated activation of ERK1/2 was significantly inhibited by H-89 (protein kinase A inhibitor), Go6983, and GF109203X (protein kinase C inhibitors) but not by U73122 (PLC inhibitor) or FIPI (PLD inhibitor). Moreover, AKHR-induced ERK1/2 phosphorylation was blocked by the calcium chelators EGTA and BAPTA-AM. Furthermore, ERK1/2 activation in both transiently and stably AKHR-expressing HEK293 cells was found to be sensitive to pretreatment of pertussis toxin, whereas AKHR-mediated ERK1/2 activation was insensitive to siRNA-induced knockdown of beta-arrestins and to pretreatment of inhibitors of EGFR, Src, and PI3K. On the basis of our data, we propose that activated AKHR signals to ERK1/2 primarily via PKA- and calcium-involved PKC-dependent pathways. Our current study provides the first in-depth study defining the mechanisms of AKH-mediated ERK activation through the Bombyx AKHR.

• 出版日期2010-12-28
• 单位浙江大学