β-adrenergic receptor activation inhibits keratinocytemigration via a cyclic adenosine monophosphate-independentmechanism

Jin Chen, Brian B. Hoffman, Roslyn Rivkah Isseroff

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

There is increasing evidence that G-protein-coupled receptors cross-talk with growth factor receptor-mediated signal transduction in a variety of cell types. We have investigated mechanisms by which the activation of β-adrenergic receptors, classically GTP-binding proteins coupled receptors, influence the migration of cultured human keratinocytes. We found that isoproterenol, a β-adrenergic receptor-selective agonist, inhibited cell migration stimulated by either epidermal growth factor, or extracellular Ca2+ in a concentration-dependent manner. This was prevented by pretreatment of the cells with the β-adrenergic receptor-selective antagonist timolol. Interestingly, isoproterenol, at a concentration of 1 nM, did not measurably increase intracellular cyclic adenosine monophosphate concentrations yet inhibited cell migration by 50%. To test further if isoproterenol's actions were mediated via activation of adenylyl cyclase, two inhibitors of its activity, 2′5′-dideoxyadenosine and SQ22536, were used. Both compounds significantly diminished isoproterenol-induced increases in intracellular cyclic adenosine monophosphate concentrations but did not attenuate isoproterenol-induced inhibition of cell migration. Also, forskolin (1 μM) markedly increased intracellular cyclic adenosine monophosphate concentrations but did not significantly inhibit cell migration. As mitogen-activated protein kinases are known to signal growth factor-stimulated cell migration, we examined whether β-adrenergic receptor-mediated inhibition of keratinocyte migration might occur via inactivation of mitogen-activated protein kinases. We found that isoproterenol inhibited phosphorylation of extracellular signal-regulated kinase mitogen-activated protein kinase in a concentration-dependent manner but had no effect on the phosphorylation of the stress mitogen-activated protein kinases c-jun N-terminal kinase and stress-activated protein kinase-2. Neither forskolin nor a membrane permeable cyclic adenosine monophosphate analog inhibited phosphorylation of any of these mitogen-activated protein kinases. These findings suggest that β-adrenergic receptor-induced inhibition of keratinocyte migration is mediated through inhibition of the extracellular signal-regulated kinase mitogen-activated protein kinase signaling in a cyclic adenosine monophosphate-independent manner.

Original languageEnglish (US)
Pages (from-to)1261-1268
Number of pages8
JournalJournal of Investigative Dermatology
Volume119
Issue number6
DOIs
StatePublished - 2002

Fingerprint

Mitogen-Activated Protein Kinases
Isoproterenol
Cyclic AMP
Adrenergic Receptors
Chemical activation
Phosphorylation
Cell Movement
Keratinocytes
Extracellular Signal-Regulated MAP Kinases
Colforsin
Mitogen-Activated Protein Kinase 11
Receptor Cross-Talk
Dideoxyadenosine
Cells
Cell Migration Inhibition
Timolol
Signal transduction
Adrenergic Agonists
Adrenergic Antagonists
Growth Factor Receptors

Keywords

  • Cell motility
  • Isoproterenol
  • Wound healing

ASJC Scopus subject areas

  • Dermatology

Cite this

β-adrenergic receptor activation inhibits keratinocytemigration via a cyclic adenosine monophosphate-independentmechanism. / Chen, Jin; Hoffman, Brian B.; Isseroff, Roslyn Rivkah.

In: Journal of Investigative Dermatology, Vol. 119, No. 6, 2002, p. 1261-1268.

Research output: Contribution to journalArticle

@article{fe35bb201e6d4cb3b95e99fff0303cb4,
title = "β-adrenergic receptor activation inhibits keratinocytemigration via a cyclic adenosine monophosphate-independentmechanism",
abstract = "There is increasing evidence that G-protein-coupled receptors cross-talk with growth factor receptor-mediated signal transduction in a variety of cell types. We have investigated mechanisms by which the activation of β-adrenergic receptors, classically GTP-binding proteins coupled receptors, influence the migration of cultured human keratinocytes. We found that isoproterenol, a β-adrenergic receptor-selective agonist, inhibited cell migration stimulated by either epidermal growth factor, or extracellular Ca2+ in a concentration-dependent manner. This was prevented by pretreatment of the cells with the β-adrenergic receptor-selective antagonist timolol. Interestingly, isoproterenol, at a concentration of 1 nM, did not measurably increase intracellular cyclic adenosine monophosphate concentrations yet inhibited cell migration by 50{\%}. To test further if isoproterenol's actions were mediated via activation of adenylyl cyclase, two inhibitors of its activity, 2′5′-dideoxyadenosine and SQ22536, were used. Both compounds significantly diminished isoproterenol-induced increases in intracellular cyclic adenosine monophosphate concentrations but did not attenuate isoproterenol-induced inhibition of cell migration. Also, forskolin (1 μM) markedly increased intracellular cyclic adenosine monophosphate concentrations but did not significantly inhibit cell migration. As mitogen-activated protein kinases are known to signal growth factor-stimulated cell migration, we examined whether β-adrenergic receptor-mediated inhibition of keratinocyte migration might occur via inactivation of mitogen-activated protein kinases. We found that isoproterenol inhibited phosphorylation of extracellular signal-regulated kinase mitogen-activated protein kinase in a concentration-dependent manner but had no effect on the phosphorylation of the stress mitogen-activated protein kinases c-jun N-terminal kinase and stress-activated protein kinase-2. Neither forskolin nor a membrane permeable cyclic adenosine monophosphate analog inhibited phosphorylation of any of these mitogen-activated protein kinases. These findings suggest that β-adrenergic receptor-induced inhibition of keratinocyte migration is mediated through inhibition of the extracellular signal-regulated kinase mitogen-activated protein kinase signaling in a cyclic adenosine monophosphate-independent manner.",
keywords = "Cell motility, Isoproterenol, Wound healing",
author = "Jin Chen and Hoffman, {Brian B.} and Isseroff, {Roslyn Rivkah}",
year = "2002",
doi = "10.1046/j.1523-1747.2002.19611.x",
language = "English (US)",
volume = "119",
pages = "1261--1268",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - β-adrenergic receptor activation inhibits keratinocytemigration via a cyclic adenosine monophosphate-independentmechanism

AU - Chen, Jin

AU - Hoffman, Brian B.

AU - Isseroff, Roslyn Rivkah

PY - 2002

Y1 - 2002

N2 - There is increasing evidence that G-protein-coupled receptors cross-talk with growth factor receptor-mediated signal transduction in a variety of cell types. We have investigated mechanisms by which the activation of β-adrenergic receptors, classically GTP-binding proteins coupled receptors, influence the migration of cultured human keratinocytes. We found that isoproterenol, a β-adrenergic receptor-selective agonist, inhibited cell migration stimulated by either epidermal growth factor, or extracellular Ca2+ in a concentration-dependent manner. This was prevented by pretreatment of the cells with the β-adrenergic receptor-selective antagonist timolol. Interestingly, isoproterenol, at a concentration of 1 nM, did not measurably increase intracellular cyclic adenosine monophosphate concentrations yet inhibited cell migration by 50%. To test further if isoproterenol's actions were mediated via activation of adenylyl cyclase, two inhibitors of its activity, 2′5′-dideoxyadenosine and SQ22536, were used. Both compounds significantly diminished isoproterenol-induced increases in intracellular cyclic adenosine monophosphate concentrations but did not attenuate isoproterenol-induced inhibition of cell migration. Also, forskolin (1 μM) markedly increased intracellular cyclic adenosine monophosphate concentrations but did not significantly inhibit cell migration. As mitogen-activated protein kinases are known to signal growth factor-stimulated cell migration, we examined whether β-adrenergic receptor-mediated inhibition of keratinocyte migration might occur via inactivation of mitogen-activated protein kinases. We found that isoproterenol inhibited phosphorylation of extracellular signal-regulated kinase mitogen-activated protein kinase in a concentration-dependent manner but had no effect on the phosphorylation of the stress mitogen-activated protein kinases c-jun N-terminal kinase and stress-activated protein kinase-2. Neither forskolin nor a membrane permeable cyclic adenosine monophosphate analog inhibited phosphorylation of any of these mitogen-activated protein kinases. These findings suggest that β-adrenergic receptor-induced inhibition of keratinocyte migration is mediated through inhibition of the extracellular signal-regulated kinase mitogen-activated protein kinase signaling in a cyclic adenosine monophosphate-independent manner.

AB - There is increasing evidence that G-protein-coupled receptors cross-talk with growth factor receptor-mediated signal transduction in a variety of cell types. We have investigated mechanisms by which the activation of β-adrenergic receptors, classically GTP-binding proteins coupled receptors, influence the migration of cultured human keratinocytes. We found that isoproterenol, a β-adrenergic receptor-selective agonist, inhibited cell migration stimulated by either epidermal growth factor, or extracellular Ca2+ in a concentration-dependent manner. This was prevented by pretreatment of the cells with the β-adrenergic receptor-selective antagonist timolol. Interestingly, isoproterenol, at a concentration of 1 nM, did not measurably increase intracellular cyclic adenosine monophosphate concentrations yet inhibited cell migration by 50%. To test further if isoproterenol's actions were mediated via activation of adenylyl cyclase, two inhibitors of its activity, 2′5′-dideoxyadenosine and SQ22536, were used. Both compounds significantly diminished isoproterenol-induced increases in intracellular cyclic adenosine monophosphate concentrations but did not attenuate isoproterenol-induced inhibition of cell migration. Also, forskolin (1 μM) markedly increased intracellular cyclic adenosine monophosphate concentrations but did not significantly inhibit cell migration. As mitogen-activated protein kinases are known to signal growth factor-stimulated cell migration, we examined whether β-adrenergic receptor-mediated inhibition of keratinocyte migration might occur via inactivation of mitogen-activated protein kinases. We found that isoproterenol inhibited phosphorylation of extracellular signal-regulated kinase mitogen-activated protein kinase in a concentration-dependent manner but had no effect on the phosphorylation of the stress mitogen-activated protein kinases c-jun N-terminal kinase and stress-activated protein kinase-2. Neither forskolin nor a membrane permeable cyclic adenosine monophosphate analog inhibited phosphorylation of any of these mitogen-activated protein kinases. These findings suggest that β-adrenergic receptor-induced inhibition of keratinocyte migration is mediated through inhibition of the extracellular signal-regulated kinase mitogen-activated protein kinase signaling in a cyclic adenosine monophosphate-independent manner.

KW - Cell motility

KW - Isoproterenol

KW - Wound healing

UR - http://www.scopus.com/inward/record.url?scp=0036907018&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036907018&partnerID=8YFLogxK

U2 - 10.1046/j.1523-1747.2002.19611.x

DO - 10.1046/j.1523-1747.2002.19611.x

M3 - Article

C2 - 12485426

AN - SCOPUS:0036907018

VL - 119

SP - 1261

EP - 1268

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

IS - 6

ER -