Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Hematopoietic Protein Tyrosine Phosphatase Mediates β2-Adrenergic Receptor-Induced Regulation of p38 Mitogen-Activated Protein Kinase in B Lymphocytes

Hematopoietic Protein Tyrosine Phosphatase Mediates β2-Adrenergic Receptor-Induced Regulation of... Hematopoietic Protein Tyrosine Phosphatase Mediates β 2 -Adrenergic Receptor-Induced Regulation of p38 Mitogen-Activated Protein Kinase in B Lymphocytes ▿ Jaclyn W. McAlees 1 , 2 and Virginia M. Sanders 2 , * 1 Integrated Biomedical Science Graduate Program 2 Department of Molecular Virology, Immunology, and Medical Genetics, the Ohio State University, 333 West 10th Avenue, Columbus, Ohio 43210 ABSTRACT Stimulation of the β 2 -adrenergic receptor (β 2 AR) on a CD40L/interleukin-4-activated B lymphocyte increases the level of immunoglobulin E (IgE) in a protein kinase A (PKA)- and p38 mitogen-activated protein kinase (MAPK)-dependent manner. However, the mechanism by which β 2 AR stimulation mediates the increase in the level of p38 MAPK activation has remained unclear. Here we show that the β 2 AR-induced increase in p38 MAPK activation occurred via a hematopoietic protein tyrosine phosphatase (HePTP)-mediated cross talk between PKA and p38 MAPK. β 2 AR agonists, cAMP-elevating agents, and PKA inhibitors were used to show that β 2 AR stimulation resulted in a PKA-dependent increase in p38 MAPK phosphorylation. Pharmacological agents and gene-deficient mice revealed that p38 MAPK phosphorylation was regulated by the G-stimulatory (Gs)/cAMP/PKA pathway independently of the G-inhibitory or β-arrestin-2 pathways. Coimmunoprecipitation and Western blot analysis showed that HePTP was phosphorylated in a PKA-dependent manner, which inactivated HePTP and allowed for increased free p38 MAPK to be phosphorylated by the MAPK cascade that was activated by CD40L. HePTP short hairpin RNA confirmed that HePTP played a role in regulating the level of p38 MAPK phosphorylation in a B cell. Thus, β 2 AR stimulation on a B cell phosphorylates and inactivates HePTP in a Gs/cAMP/PKA-dependent manner to release bound p38 MAPK, making more available for phosphorylation and subsequent IgE regulation. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Molecular and Cellular Biology American Society For Microbiology

Hematopoietic Protein Tyrosine Phosphatase Mediates β2-Adrenergic Receptor-Induced Regulation of p38 Mitogen-Activated Protein Kinase in B Lymphocytes

Hematopoietic Protein Tyrosine Phosphatase Mediates β2-Adrenergic Receptor-Induced Regulation of p38 Mitogen-Activated Protein Kinase in B Lymphocytes

Molecular and Cellular Biology , Volume 29 (3): 675 – Feb 1, 2009

Abstract

Hematopoietic Protein Tyrosine Phosphatase Mediates β 2 -Adrenergic Receptor-Induced Regulation of p38 Mitogen-Activated Protein Kinase in B Lymphocytes ▿ Jaclyn W. McAlees 1 , 2 and Virginia M. Sanders 2 , * 1 Integrated Biomedical Science Graduate Program 2 Department of Molecular Virology, Immunology, and Medical Genetics, the Ohio State University, 333 West 10th Avenue, Columbus, Ohio 43210 ABSTRACT Stimulation of the β 2 -adrenergic receptor (β 2 AR) on a CD40L/interleukin-4-activated B lymphocyte increases the level of immunoglobulin E (IgE) in a protein kinase A (PKA)- and p38 mitogen-activated protein kinase (MAPK)-dependent manner. However, the mechanism by which β 2 AR stimulation mediates the increase in the level of p38 MAPK activation has remained unclear. Here we show that the β 2 AR-induced increase in p38 MAPK activation occurred via a hematopoietic protein tyrosine phosphatase (HePTP)-mediated cross talk between PKA and p38 MAPK. β 2 AR agonists, cAMP-elevating agents, and PKA inhibitors were used to show that β 2 AR stimulation resulted in a PKA-dependent increase in p38 MAPK phosphorylation. Pharmacological agents and gene-deficient mice revealed that p38 MAPK phosphorylation was regulated by the G-stimulatory (Gs)/cAMP/PKA pathway independently of the G-inhibitory or β-arrestin-2 pathways. Coimmunoprecipitation and Western blot analysis showed that HePTP was phosphorylated in a PKA-dependent manner, which inactivated HePTP and allowed for increased free p38 MAPK to be phosphorylated by the MAPK cascade that was activated by CD40L. HePTP short hairpin RNA confirmed that HePTP played a role in regulating the level of p38 MAPK phosphorylation in a B cell. Thus, β 2 AR stimulation on a B cell phosphorylates and inactivates HePTP in a Gs/cAMP/PKA-dependent manner to release bound p38 MAPK, making more available for phosphorylation and subsequent IgE regulation.

Loading next page...
 
/lp/american-society-for-microbiology/hematopoietic-protein-tyrosine-phosphatase-mediates-2-adrenergic-uD34Ek2070

References (67)

Publisher
American Society For Microbiology
Copyright
Copyright © 2009 by the American society for Microbiology.
ISSN
0270-7306
eISSN
1098-5549
DOI
10.1128/MCB.01466-08
pmid
19047375
Publisher site
See Article on Publisher Site

Abstract

Hematopoietic Protein Tyrosine Phosphatase Mediates β 2 -Adrenergic Receptor-Induced Regulation of p38 Mitogen-Activated Protein Kinase in B Lymphocytes ▿ Jaclyn W. McAlees 1 , 2 and Virginia M. Sanders 2 , * 1 Integrated Biomedical Science Graduate Program 2 Department of Molecular Virology, Immunology, and Medical Genetics, the Ohio State University, 333 West 10th Avenue, Columbus, Ohio 43210 ABSTRACT Stimulation of the β 2 -adrenergic receptor (β 2 AR) on a CD40L/interleukin-4-activated B lymphocyte increases the level of immunoglobulin E (IgE) in a protein kinase A (PKA)- and p38 mitogen-activated protein kinase (MAPK)-dependent manner. However, the mechanism by which β 2 AR stimulation mediates the increase in the level of p38 MAPK activation has remained unclear. Here we show that the β 2 AR-induced increase in p38 MAPK activation occurred via a hematopoietic protein tyrosine phosphatase (HePTP)-mediated cross talk between PKA and p38 MAPK. β 2 AR agonists, cAMP-elevating agents, and PKA inhibitors were used to show that β 2 AR stimulation resulted in a PKA-dependent increase in p38 MAPK phosphorylation. Pharmacological agents and gene-deficient mice revealed that p38 MAPK phosphorylation was regulated by the G-stimulatory (Gs)/cAMP/PKA pathway independently of the G-inhibitory or β-arrestin-2 pathways. Coimmunoprecipitation and Western blot analysis showed that HePTP was phosphorylated in a PKA-dependent manner, which inactivated HePTP and allowed for increased free p38 MAPK to be phosphorylated by the MAPK cascade that was activated by CD40L. HePTP short hairpin RNA confirmed that HePTP played a role in regulating the level of p38 MAPK phosphorylation in a B cell. Thus, β 2 AR stimulation on a B cell phosphorylates and inactivates HePTP in a Gs/cAMP/PKA-dependent manner to release bound p38 MAPK, making more available for phosphorylation and subsequent IgE regulation.

Journal

Molecular and Cellular BiologyAmerican Society For Microbiology

Published: Feb 1, 2009

There are no references for this article.