PMID- 19047375
OWN - NLM
STAT- MEDLINE
DCOM- 20090204
LR  - 20211020
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 29
IP  - 3
DP  - 2009 Feb
TI  - Hematopoietic protein tyrosine phosphatase mediates beta2-adrenergic 
      receptor-induced regulation of p38 mitogen-activated protein kinase in B 
      lymphocytes.
PG  - 675-86
LID - 10.1128/MCB.01466-08 [doi]
AB  - Stimulation of the beta(2)-adrenergic receptor (beta(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 beta(2)AR stimulation 
      mediates the increase in the level of p38 MAPK activation has remained unclear. 
      Here we show that the beta(2)AR-induced increase in p38 MAPK activation occurred 
      via a hematopoietic protein tyrosine phosphatase (HePTP)-mediated cross talk 
      between PKA and p38 MAPK. beta(2)AR agonists, cAMP-elevating agents, and PKA 
      inhibitors were used to show that beta(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 
      beta-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, 
      beta(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.
FAU - McAlees, Jaclyn W
AU  - McAlees JW
AD  - Department of Molecular Virology, The Ohio State University, Columbus, Ohio 
      43210, USA.
FAU - Sanders, Virginia M
AU  - Sanders VM
LA  - eng
GR  - R01 AI037326/AI/NIAID NIH HHS/United States
GR  - T32 AI055411/AI/NIAID NIH HHS/United States
GR  - T32 AI-55411/AI/NIAID NIH HHS/United States
GR  - NIH-AI-37326/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20081201
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Arrb2 protein, mouse)
RN  - 0 (Arrestins)
RN  - 0 (Creb1 protein, mouse)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Receptors, Adrenergic, beta-2)
RN  - 0 (beta-Arrestin 2)
RN  - 0 (beta-Arrestins)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases, Non-Receptor)
RN  - EC 3.1.3.48 (Ptpn7 protein, mouse)
RN  - EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gi-Go)
RN  - EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gs)
SB  - IM
MH  - Animals
MH  - Arrestins/metabolism
MH  - B-Lymphocytes/*enzymology
MH  - Cell Line
MH  - Cyclic AMP/metabolism
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/metabolism
MH  - Female
MH  - GTP-Binding Protein alpha Subunits, Gi-Go/metabolism
MH  - GTP-Binding Protein alpha Subunits, Gs/metabolism
MH  - Immunoglobulin E/metabolism
MH  - Immunoglobulin G/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Models, Biological
MH  - Phosphorylation
MH  - Protein Tyrosine Phosphatases, Non-Receptor/*metabolism
MH  - Receptors, Adrenergic, beta-2/*metabolism
MH  - beta-Arrestin 2
MH  - beta-Arrestins
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
PMC - PMC2630696
EDAT- 2008/12/03 09:00
MHDA- 2009/02/05 09:00
PMCR- 2009/08/01
CRDT- 2008/12/03 09:00
PHST- 2008/12/03 09:00 [pubmed]
PHST- 2009/02/05 09:00 [medline]
PHST- 2008/12/03 09:00 [entrez]
PHST- 2009/08/01 00:00 [pmc-release]
AID - MCB.01466-08 [pii]
AID - 1466-08 [pii]
AID - 10.1128/MCB.01466-08 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2009 Feb;29(3):675-86. doi: 10.1128/MCB.01466-08. Epub 2008 Dec 1.