Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
51
pubmed:dateCreated
2010-12-21
pubmed:abstractText
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 ?-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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1520-4995
pubmed:author
pubmed:issnType
Electronic
pubmed:day
28
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10862-72
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Bombyx adipokinetic hormone receptor activates extracellular signal-regulated kinase 1 and 2 via G protein-dependent PKA and PKC but ?-arrestin-independent pathways.
pubmed:affiliation
Institute of Biochemistry, College of Life Sciences, Zijingang Campus, Zhejiang University, Hangzhou, Zhejiang 310058, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural