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Src-mediated tyrosine phosphorylation of dynamin is required for beta2-adrenergic receptor internalization and mitogen-activated protein kinase signaling.

Publication ,  Journal Article
Ahn, S; Maudsley, S; Luttrell, LM; Lefkowitz, RJ; Daaka, Y
Published in: J Biol Chem
January 15, 1999

Some forms of G protein-coupled receptor signaling, such as activation of mitogen-activated protein kinase cascade as well as resensitization of receptors after hormone-induced desensitization, require receptor internalization via dynamin-dependent clathrin-coated pit mechanisms. Here we demonstrate that activation of beta2-adrenergic receptors (beta2-ARs) leads to c-Src-mediated tyrosine phosphorylation of dynamin, which is required for receptor internalization. Two tyrosine residues, Tyr231 and Tyr597, are identified as the major phosphorylation sites. Mutation of these residues to phenylalanine dramatically decreases the c-Src-mediated phosphorylation of dynamin following beta2-AR stimulation. Moreover, expression of Y231F/Y597F dynamin inhibits beta2-AR internalization and the isoproterenol-stimulated mitogen-activated protein kinase activation. Thus, agonist-induced, c-Src-mediated tyrosine phosphorylation of dynamin is essential for its function in clathrin mediated G protein-coupled receptor endocytosis.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

January 15, 1999

Volume

274

Issue

3

Start / End Page

1185 / 1188

Location

United States

Related Subject Headings

  • src-Family Kinases
  • src Homology Domains
  • Tyrosine
  • Signal Transduction
  • Receptors, Adrenergic, beta-2
  • Protein-Tyrosine Kinases
  • Phosphorylation
  • Microtubules
  • Humans
  • GTP Phosphohydrolases
 

Citation

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Ahn, S., Maudsley, S., Luttrell, L. M., Lefkowitz, R. J., & Daaka, Y. (1999). Src-mediated tyrosine phosphorylation of dynamin is required for beta2-adrenergic receptor internalization and mitogen-activated protein kinase signaling. J Biol Chem, 274(3), 1185–1188. https://doi.org/10.1074/jbc.274.3.1185
Ahn, S., S. Maudsley, L. M. Luttrell, R. J. Lefkowitz, and Y. Daaka. “Src-mediated tyrosine phosphorylation of dynamin is required for beta2-adrenergic receptor internalization and mitogen-activated protein kinase signaling.J Biol Chem 274, no. 3 (January 15, 1999): 1185–88. https://doi.org/10.1074/jbc.274.3.1185.
Ahn, S., et al. “Src-mediated tyrosine phosphorylation of dynamin is required for beta2-adrenergic receptor internalization and mitogen-activated protein kinase signaling.J Biol Chem, vol. 274, no. 3, Jan. 1999, pp. 1185–88. Pubmed, doi:10.1074/jbc.274.3.1185.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

January 15, 1999

Volume

274

Issue

3

Start / End Page

1185 / 1188

Location

United States

Related Subject Headings

  • src-Family Kinases
  • src Homology Domains
  • Tyrosine
  • Signal Transduction
  • Receptors, Adrenergic, beta-2
  • Protein-Tyrosine Kinases
  • Phosphorylation
  • Microtubules
  • Humans
  • GTP Phosphohydrolases