scholarly journals G-protein-coupled Receptor Stimulation of the p42/p44 Mitogen-activated Protein Kinase Pathway Is Attenuated by Lipid Phosphate Phosphatases 1, 1a, and 2 in Human Embryonic Kidney 293 Cells

2001 ◽  
Vol 276 (16) ◽  
pp. 13452-13460 ◽  
Author(s):  
Forbes Alderton ◽  
Peter Darroch ◽  
Balwinder Sambi ◽  
Amanda McKie ◽  
Ikhlas Said Ahmed ◽  
...  
Keyword(s):  
Mitogen Activated Protein Kinase ◽  
Human Embryonic Kidney ◽  
Receptor Stimulation ◽  
293 Cells ◽  
Mitogen Activated Protein ◽  
Lipid Phosphate ◽  
Lipid Phosphate Phosphatases ◽  
G Protein Coupled ◽  
Kinase Pathway ◽  
Stimulation Of

scholarly journals G Protein-Coupled Receptor-Mediated Mitogen-Activated Protein Kinase Activation through Cooperation of Gαq and Gαi Signals

2000 ◽  
Vol 20 (18) ◽  
pp. 6837-6848 ◽  
Author(s):  
Andree Blaukat ◽  
Ana Barac ◽  
Michael J. Cross ◽  
Stefan Offermanns ◽  
Ivan Dikic
Keyword(s):  
Protein Kinase ◽  
G Protein ◽  
Tyrosine Kinases ◽  
Synergistic Effects ◽  
Mitogen Activated Protein Kinase ◽  
General Mechanism ◽  
Mitogen Activated Protein ◽  
Novel Concept ◽  
G Protein Coupled ◽  
Stimulation Of

ABSTRACT G protein-coupled receptors (GPCRs) have been shown to stimulate extracellular regulated kinases (ERKs) through a number of linear pathways that are initiated by Gq/11 or Giproteins. We studied signaling to the ERK cascade by receptors that simultaneously activate both G protein subfamilies. In HEK293T cells, bradykinin B2 receptor (B2R)-induced stimulation of ERK2 and transcriptional activity of Elk1 are dependent on Gαq-mediated protein kinase C (PKC) and on Gαi-induced Ras activation, while they are independent of Gβγ subunits, phosphatidylinositol 3-kinase, and tyrosine kinases. Similar results were obtained with m1 and m3muscarinic receptors in HEK293T cells and with the B2R in human and mouse fibroblasts, indicating a general mechanism in signaling toward the ERK cascade. Furthermore, the bradykinin-induced activation of ERK is strongly reduced in Gαq/11-deficient fibroblasts. In addition, we found that constitutively active mutants of Gαq/11 or Gαi proteins alone poorly stimulate ERK2, whereas a combination of both led to synergistic effects. We conclude that dually coupled GPCRs require a cooperation of Gαi- and Gq/11-mediated pathways for efficient stimulation of the ERK cascade. Cooperative signaling by multiple G proteins thus might represent a novel concept implicated in the regulation of cellular responses by GPCRs.

scholarly journals Proinsulin C-peptide activates cAMP response element-binding proteins through the p38 mitogen-activated protein kinase pathway in mouse lung capillary endothelial cells

2002 ◽  
Vol 366 (3) ◽  
pp. 737-744 ◽  
Author(s):  
Takanori KITAMURA ◽  
Kazuhiro KIMURA ◽  
Bae Dong JUNG ◽  
Kennedy MAKONDO ◽  
Naoki SAKANE ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Mouse Lung ◽  
Camp Response Element ◽  
Site Specific ◽  
C Peptide ◽  
Mitogen Activated Protein ◽  
Capillary Endothelial Cells ◽  
Kinase Pathway ◽  
Stimulation Of

Proinsulin C-peptide has been reported to have some biological activities and to be possibly involved in the development of diabetic microangiopathy. In the present study, we examined the effects of C-peptide on the mitogen-activated protein kinase pathway in LEII mouse lung capillary endothelial cells. Stimulation of the cells with C-peptide increased both p38 mitogen-activated protein kinase (p38MAPK) and extracellular signal-regulated kinase (ERK1/2) activities and activity-related site-specific phosphorylation of the respective kinases in a concentration-dependent manner, but failed to activate c-Jun N-terminal kinase. Stimulation of the cells with C-peptide also induced site-specific phosphorylation of cAMP response element (CRE)-binding protein (CREB)/activating transcription factor 1 (ATF1), and thereby binding of these transcription factors to CRE. Among three CREB kinases tested, phosphorylation of mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP-K2) was induced after stimulation with C-peptide. The phosphorylation of CREB, ATF1 and MAPKAP-K2 were inhibited by SB203580, a p38MAPK inhibitor, but not by PD98059, an ERK kinase inhibitor. These results indicate that C-peptide activates p38MAPK followed by MAPKAP-K2 to enhance DNA—CREB/ATF1 interactions.

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