PP2A activation by β2-adrenergic receptor agonists: Novel regulatory mechanism of keratinocyte migration

Christine E. Pullar, Jin Chen, Roslyn Rivkah Isseroff

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Understanding the mechanisms that regulate cell migration is important for devising novel therapies to control metastasis or enhance wound healing. Previously, we demonstrated that β2-adrenergic receptor (β2-AR) activation in keratinocytes inhibited their migration by decreasing the phosphorylation of a critical promigratory signaling component, the extracellular signal-related kinase (ERK). Here we demonstrate that β2-AR-induced inhibition of migration is mediated by the activation of the serine/threonine phosphatase PP2A. Pretreating human keratinocytes with the PP2A inhibitor, okadaic acid, prevented the β2-AR-induced inhibition of migration, either as isolated cells or as a confluent sheet of cells repairing an in vitro "wound" and also prevented the β2-AR-induced reduction in ERK phosphorylation. Similar results were obtained with human corneal epithelial cells. In keratinocytes, immunoprecipitation studies revealed that β2-AR activation resulted in the rapid association of β2-AR with PP2A as well as a 37% increase in association of PP2A with ERK2. Finally, β2-AR activation resulted in a rapid and transient 2-fold increase in PP2A activity. Thus, we provide the first evidence that β2-AR activation in keratinocytes modulates migration via a novel pathway utilizing PP2A to alter the promigratory signaling cascade. Exploiting this pathway may result in novel therapeutic approaches for control of epithelial cell migration.

Original languageEnglish (US)
Pages (from-to)22555-22562
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number25
DOIs
StatePublished - Jun 20 2003

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Adrenergic Agonists
Keratinocytes
Adrenergic Receptors
Chemical activation
Phosphorylation
Cell Movement
Phosphotransferases
Epithelial Cells
Association reactions
Okadaic Acid
Phosphoprotein Phosphatases
Immunoprecipitation
Wound Healing
Neoplasm Metastasis
Wounds and Injuries
Therapeutics

ASJC Scopus subject areas

  • Biochemistry

Cite this

PP2A activation by β2-adrenergic receptor agonists : Novel regulatory mechanism of keratinocyte migration. / Pullar, Christine E.; Chen, Jin; Isseroff, Roslyn Rivkah.

In: Journal of Biological Chemistry, Vol. 278, No. 25, 20.06.2003, p. 22555-22562.

Research output: Contribution to journalArticle

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