Distinct roles for Src tyrosine kinase in β2-adrenergic receptor signaling to MAPK and in receptor internalization

Jianyun Huang, Yutong Sun, Xin Yun Huang

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)21637-21642
Number of pages6
JournalJournal of Biological Chemistry
Volume279
Issue number20
DOIs
StatePublished - May 14 2004

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TYK2 Kinase
src-Family Kinases
Mitogen-Activated Protein Kinases
Adrenergic Receptors
Fibroblasts
Chemical activation
Arrestin
Mitogen-Activated Protein Kinase 1
G-Protein-Coupled Receptors
Ligands
HEK293 Cells
Endocytosis
Cells

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Distinct roles for Src tyrosine kinase in β2-adrenergic receptor signaling to MAPK and in receptor internalization. / Huang, Jianyun; Sun, Yutong; Huang, Xin Yun.

In: Journal of Biological Chemistry, Vol. 279, No. 20, 14.05.2004, p. 21637-21642.

Research output: Contribution to journalArticle

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