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Stimulation of mitogen-activated protein kinase by G protein-coupled alpha(2)-adrenergic receptors does not require agonist-elicited endocytosis.

Publication ,  Journal Article
Schramm, NL; Limbird, LE
Published in: The Journal of biological chemistry
August 1999

Agonist-elicited receptor sequestration is strikingly different for the alpha(2A)- versus alpha(2B)-adrenergic receptor (alpha(2)-AR) subtypes; the alpha(2B)-AR undergoes rapid and extensive disappearance from the HEK 293 cell surface, whereas the alpha(2A)-AR does not (Daunt, D. A., Hurt, C., Hein, L., Kallio, J., Feng, F., and Kobilka, B. K. (1997) Mol. Pharmacol. 51, 711-720; Eason, M. G., and Liggett, S. B. (1992) J. Biol. Chem. 267, 25473-25479). Since recent reports suggest that endocytosis is required for some G protein-coupled receptors to stimulate the mitogen-activated protein (MAP) kinase cascade (Daaka, Y., Luttrell, L. M., Ahn, S., Della Rocca, G. J., Ferguson, S. S., Caron, M. G., and Lefkowitz, R. J. (1998) J. Biol. Chem. 273, 685-688; Luttrell, L. M., Daaka, Y., Della Rocca, G. J., and Lefkowitz, R. J. (1997) J. Biol. Chem. 272, 31648-31656; Ignatova, E. G., Belcheva, M. M., Bohn, L. M., Neuman, M. C., and Coscia, C. J. (1999) J. Neurosci. 19, 56-63), we evaluated the differential ability of these two subtypes to activate MAP kinase. We observed no correlation between subtype-dependent agonist-elicited receptor redistribution and receptor activation of the MAP kinase cascade. Furthermore, incubation of cells with K(+)-depleted medium eliminated alpha(2B)-AR internalization but did not eliminate MAP kinase activation, suggesting that receptor internalization is not a general prerequisite for activation of the MAP kinase cascade via G(i)-coupled receptors. We also noted that neither dominant negative dynamin (K44A) nor concanavalin A treatment dramatically altered MAP kinase activation or receptor redistribution, indicating that these experimental tools do not universally block G protein-coupled receptor internalization.

Duke Scholars

Published In

The Journal of biological chemistry

DOI

EISSN

1083-351X

ISSN

0021-9258

Publication Date

August 1999

Volume

274

Issue

35

Start / End Page

24935 / 24940

Related Subject Headings

  • Transfection
  • Receptors, Adrenergic, alpha-2
  • Humans
  • GTP-Binding Proteins
  • GTP Phosphohydrolases
  • Epinephrine
  • Enzyme Activation
  • Endocytosis
  • Dynamins
  • Concanavalin A
 

Citation

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Schramm, N. L., & Limbird, L. E. (1999). Stimulation of mitogen-activated protein kinase by G protein-coupled alpha(2)-adrenergic receptors does not require agonist-elicited endocytosis. The Journal of Biological Chemistry, 274(35), 24935–24940. https://doi.org/10.1074/jbc.274.35.24935
Schramm, N. L., and L. E. Limbird. “Stimulation of mitogen-activated protein kinase by G protein-coupled alpha(2)-adrenergic receptors does not require agonist-elicited endocytosis.The Journal of Biological Chemistry 274, no. 35 (August 1999): 24935–40. https://doi.org/10.1074/jbc.274.35.24935.
Schramm, N. L., and L. E. Limbird. “Stimulation of mitogen-activated protein kinase by G protein-coupled alpha(2)-adrenergic receptors does not require agonist-elicited endocytosis.The Journal of Biological Chemistry, vol. 274, no. 35, Aug. 1999, pp. 24935–40. Epmc, doi:10.1074/jbc.274.35.24935.

Published In

The Journal of biological chemistry

DOI

EISSN

1083-351X

ISSN

0021-9258

Publication Date

August 1999

Volume

274

Issue

35

Start / End Page

24935 / 24940

Related Subject Headings

  • Transfection
  • Receptors, Adrenergic, alpha-2
  • Humans
  • GTP-Binding Proteins
  • GTP Phosphohydrolases
  • Epinephrine
  • Enzyme Activation
  • Endocytosis
  • Dynamins
  • Concanavalin A