scholarly journals Stimulation of Mitogen-activated Protein Kinase by G Protein-coupled α2-Adrenergic Receptors Does Not Require Agonist-elicited Endocytosis

1999 ◽  
Vol 274 (35) ◽  
pp. 24935-24940 ◽  
Author(s):  
Nicole L. Schramm ◽  
Lee E. Limbird
Keyword(s):  
Protein Kinase ◽  
G Protein ◽  
Adrenergic Receptors ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
G Protein Coupled ◽  
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.

Role of endocytosis in signalling and regulation of G-protein-coupled receptors

2001 ◽  
Vol 29 (4) ◽  
pp. 500-504 ◽  
Author(s):  
M. von Zastrow
Keyword(s):  
G Protein ◽  
Adrenergic Receptors ◽  
G Protein Coupled Receptors ◽  
Mitogen Activated Protein Kinase ◽  
Vesicular Carriers ◽  
Mitogen Activated Protein ◽  
Effector Pathways ◽  
Endocytic Vesicles ◽  
G Protein Coupled

Many G-protein-coupled receptors (GPCRs) undergo agonist-induced endocytosis. Endocytosis contributes to distinct processes that regulate the number and functional activity of receptors present in the plasma membrane, contributing to the well described processes of receptor sequestration and down-regulation. Emerging evidence suggests additional functions of endocytosis in mediating GPCR signalling via certain effector pathways, such as mitogen-activated protein kinase modules. The diverse functions of endocytosis raise fundamental questions about the nature of the vesicular carriers and membrane pathways that mediate the endocytic trafficking of specific GPCRs. Insights into the biochemical and functional properties of endocytic vesicles containing internalized opioid and adrenergic receptors will be discussed. Progress towards understanding the mechanisms that control the specificity with which distinct GPCRs are sorted to specialized sub-populations of endocytic vesicles will be highlighted.

scholarly journals Ras-dependent Mitogen-activated Protein Kinase Activation by G Protein-coupled Receptors

1997 ◽  
Vol 272 (31) ◽  
pp. 19125-19132 ◽  
Author(s):  
Gregory J. Della Rocca ◽  
Tim van Biesen ◽  
Yehia Daaka ◽  
Deirdre K. Luttrell ◽  
Louis M. Luttrell ◽  
...  
Keyword(s):  
Protein Kinase ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Mitogen Activated Protein Kinase ◽  
Kinase Activation ◽  
Protein Kinase Activation ◽  
Mitogen Activated Protein ◽  
G Protein Coupled
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