TY - JOUR
T1 - Distinct roles for Src tyrosine kinase in β2-adrenergic receptor signaling to MAPK and in receptor internalization
AU - Huang, Jianyun
AU - Sun, Yutong
AU - Huang, Xin Yun
PY - 2004/5/14
Y1 - 2004/5/14
N2 - G protein-coupled receptors form the largest family of membrane receptors and transmit diverse ligand signals to modulate various cellular responses. After activation by their ligands, some of these G protein-coupled receptors are desensitized, internalized (endocytosed), and down-regulated (degraded). In HEK 293 cells, the Gs-coupled β2-adrenergic receptor was postulated to initiate a second wave of signaling, such as the activation of the mitogen-activated protein kinase (MAPK) pathway after the receptor is internalized. The tyrosine kinase c-Src plays a critical role in these events. Here we used mouse embryonic fibroblast (MEF) cells deficient in Src family tyrosine kinases to examine the role of Src in β2-adrenergic receptor signaling to the MAPK pathway and in receptor internalization. We found that in Src-deficient cells the β2-adrenergic receptor could activate the MAPK pathway. However, the internalization of β 2-adrenergic receptors was blocked in Src-deficient MEF cells. Furthermore, we observed that in MEF cells deficient in β-arrestin 2 the internalization of the β2-adrenergic receptor was impaired, whereas the activation of the MAPK pathway by the β2-adrenergic receptor was normal. Our data demonstrate that although Src and β-arrestin 2 play essential roles in β2-adrenergic receptor internalization, they are not required for the activation of the MAPK pathway by the β2-adrenergic receptor. In other words, our finding suggests that receptor internalization is not required for β 2-adrenergic receptor signaling to the MAPK pathway in MEF cells.
AB - G protein-coupled receptors form the largest family of membrane receptors and transmit diverse ligand signals to modulate various cellular responses. After activation by their ligands, some of these G protein-coupled receptors are desensitized, internalized (endocytosed), and down-regulated (degraded). In HEK 293 cells, the Gs-coupled β2-adrenergic receptor was postulated to initiate a second wave of signaling, such as the activation of the mitogen-activated protein kinase (MAPK) pathway after the receptor is internalized. The tyrosine kinase c-Src plays a critical role in these events. Here we used mouse embryonic fibroblast (MEF) cells deficient in Src family tyrosine kinases to examine the role of Src in β2-adrenergic receptor signaling to the MAPK pathway and in receptor internalization. We found that in Src-deficient cells the β2-adrenergic receptor could activate the MAPK pathway. However, the internalization of β 2-adrenergic receptors was blocked in Src-deficient MEF cells. Furthermore, we observed that in MEF cells deficient in β-arrestin 2 the internalization of the β2-adrenergic receptor was impaired, whereas the activation of the MAPK pathway by the β2-adrenergic receptor was normal. Our data demonstrate that although Src and β-arrestin 2 play essential roles in β2-adrenergic receptor internalization, they are not required for the activation of the MAPK pathway by the β2-adrenergic receptor. In other words, our finding suggests that receptor internalization is not required for β 2-adrenergic receptor signaling to the MAPK pathway in MEF cells.
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U2 - 10.1074/jbc.M400956200
DO - 10.1074/jbc.M400956200
M3 - Article
C2 - 14990578
AN - SCOPUS:2442714117
SN - 0021-9258
VL - 279
SP - 21637
EP - 21642
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 20
ER -