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Arrestin serves as a molecular switch, linking endogenous alpha2‐adrenergic receptor to Src‐dependent but not Src‐independent ERK activation
Author(s) -
Wang Qin,
Zhao Jiali,
Limbird Lee
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a254-b
Subject(s) - mapk/erk pathway , proto oncogene tyrosine protein kinase src , arrestin , microbiology and biotechnology , phosphorylation , signal transduction , receptor , kinase , endogeny , biology , chemistry , g protein coupled receptor , endocrinology , biochemistry
Our previous studies have demonstrated that neither receptor endocytosis nor arrestin is required for ERK activation by the α 2 ‐adrenergic receptor (AR) (Wang et. al., Science 304, 1940). In this paper we address whether arrestin plays a role in determining the route of α 2 AR‐evoked ERK signaling activation, taking advantage of endogenous expression of the α 2A AR subtype in mouse embryonic fibroblasts (MEFs) and the availability of MEFs without arrestin expression (derived from Arr2,3 −/− mice). Our data demonstrate that endogenous α 2A AR evokes ERK phosphorylation through Src‐dependent and Src‐independent pathway, both of which are G protein‐dependent and converge to the Ras‐Raf‐MEK pathway. Arrestin is essential to recruit Src to this process, as Src is not required in α 2A AR‐mediated ERK signaling in Arr2,3 −/− MEFs. Although α 2 ‐agonists have similar potencies in stimulating Src‐dependent and –independent ERK phosphorylation in WT and Arr2,3 −/− cells, respectively, the Src‐ in dependent α 2A AR‐mediated ERK activation has a longer duration and phospho‐ERK is more rapidly translocated into nuclei when compared to Src‐dependent activation. These data not only affirm the role of arrestin as an escort for signaling molecules such as Src family kinase, but also demonstrates the impact of this modulation on both the temporal and spatial properties of ERK activation.