G Protein-coupled Receptors Mediate Two Functionally Distinct Pathways of Tyrosine Phosphorylation in Rat 1a Fibroblasts

Luttrell, Louis M.; Daaka, Yehia; Rocca, Gregory J. Della; Lefkowitz, Robert J.

doi:10.1074/jbc.272.50.31648

Cited by 194 publications

(153 citation statements)

References 48 publications

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“…This indicates that for the $,-adrenergic, and perhaps for other G,-coupled GPCRs, activation of the Ras-MAPK pathway occurs in an identical manner to that seen for other Gi-coupled GPCRs. Luttrell et al, 1997a). These results suggest that GPCR endocytosis is a necessa.…”

Section: Grb2 and L A D S To Ras Activation (Kraneneburg Etmentioning

confidence: 62%

SH3 Binding Domains in the Dopamine D4 Receptor

Oldenhof

Vickery²,

Anafi³

et al. 1998

Biochemistry

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The dopamine D4 receptor is a G protein-coupled receptor (GPCR) that belongs to the dopamine D2-like receptor family. Functionally, the D2-like receptors are characterized by their ability to inhibit adenylyl cyclase. The dopamine D4 receptor as well as many other catecholaminergic receptors contain several putative SH3 binding domains. Most of these sites in the D4 receptor are located in a polymorphic repeat sequence and flanking sequences in the third intracellular loop. Here we demonstrate that this region of the D4 receptor can interact with a large variety of SH3 domains of different origin. The strongest interactions were seen with the SH2−SH3 adapter proteins Grb2 and Nck. The repeat sequence itself is not essential in this interaction. The data presented indicate that the different SH3 domains in the adapter proteins interact in a cooperative fashion with two distinct sites immediately upstream and downstream from the repeat sequence. Removal of all the putative SH3 binding domains in the third intracellular loop of the dopamine D4 receptor resulted in a receptor that could still bind spiperone and dopamine. Dopamine could not modulate the coupling of these mutant receptors to adenylyl cyclase and MAPK, although dopamine modulated receptor−G protein interaction appeared normal. The receptor deletion mutants show strong constitutive internalization that may account for the deficiency in functional activation of second messengers. The data indicates that the D4 receptor contains SH3 binding sites and that these sites fall within a region involved in the control of receptor internalization.

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Section: Grb2 and L A D S To Ras Activation (Kraneneburg Etmentioning

confidence: 62%

SH3 Binding Domains in the Dopamine D4 Receptor

Oldenhof

Vickery²,

Anafi³

et al. 1998

Biochemistry

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“…The non-receptor tyrosine kinase Src (and probably Src family members) regulates a myriad of signalling pathways, including those of GPCRs [63,64]. Src has been shown to be critical to β 2 AR sequestration in response to stimulation by either β-agonist [65][66][67] or insulin [24]. There are several potential docking sites for Src within the AKAP250/β 2 AR signalling complex.…”

Section: Pxxp Domains and Srcmentioning

confidence: 99%

AKAPs (A-kinase anchoring proteins) and molecules that compose their G-protein-coupled receptor signalling complexes

Malbon

Tao

Wang

2004

Biochemical Journal

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Cell signalling mediated via GPCRs (G-protein-coupled receptors) is a major paradigm in biology, involving the assembly of receptors, G-proteins, effectors and downstream elements into complexes that approach in design 'solid-state' signalling devices. Scaffold molecules, such as the AKAPs (A-kinase anchoring proteins), were discovered more than a decade ago and represent dynamic platforms, enabling multivalent signalling. AKAP79 and AKAP250 were the first to be shown to bind to membrane-embedded GPCRs, orchestrating the interactions of various protein kinases (including tyrosine kinases), protein phosphatases (e.g. calcineurin) and cytoskeletal elements with at least one member of the superfamily of GPCRs, the prototypical β 2 -adrenergic receptor. In this review, the multivalent interactions of AKAP250 with the cell membrane, receptor, cytoskeleton and constituent components are detailed, providing a working model for AKAP-based GPCR signalling complexes. Dynamic regulation of the AKAP-receptor complex is mediated by ordered protein phosphorylation.

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“…Receptor endocytosis and G␣ i protein activation have already been demonstrated as important contributors for the activation of different kinases, including Src kinases, by different GPCRs (16,18,20,43). Moreover, Src family kinases have been shown to mediate certain neutrophil functions.…”

Section: Src Family Kinases But Not Jak2 P38 Kinase or Mek/erk Kinmentioning

confidence: 99%

“…Because Src kinases can be associated with GPCR endocytosis (16,27), we investigated whether both events could, in a dependent or independent manner, be involved in neutrophil degranulation in response to LTB 4 . Degranulation is one of the most important biological activities of neutrophils.…”

Section: Involvement Of Blt1 Endocytosis and Yes Kinase Activation Inmentioning

confidence: 99%

Involvement of BLT1 Endocytosis and Yes Kinase Activation in Leukotriene B4-Induced Neutrophil Degranulation

Gaudreault

Thompson

Staňková

et al. 2005

The Journal of Immunology

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One of the important biological activities of human neutrophils is degranulation, which can be induced by leukotriene B4 (LTB4). Here we investigated the intracellular signaling events involved in neutrophil degranulation mediated by the high affinity LTB4 receptor, BLT1. Peripheral blood neutrophils as well as the promyeloid PLB-985 cell line, stably transfected with BLT1 cDNA and differentiated into a neutrophil-like cell phenotype, were used throughout this study. LTB4-induced enzyme release was inhibited by 50–80% when cells were pretreated with the pharmacological inhibitors of endocytosis sucrose, Con A and NH4Cl. In addition, transient transfection with a dominant negative form of dynamin (K44A) resulted in ∼70% inhibition of ligand-induced degranulation. Pretreating neutrophils or BLT1-expressing PLB-985 cells with the Src family kinase inhibitor PP1 resulted in a 30–60% inhibition in BLT1-mediated degranulation. Yes kinase, but not c-Src, Fgr, Hck, or Lyn, was found to exhibit up-regulated kinase activity after LTB4 stimulation. Moreover, BLT1 endocytosis was found to be necessary for Yes kinase activation in neutrophils. LTB4-induced degranulation was also sensitive to inhibition of PI3K. In contrast, it was not affected by inhibition of the mitogen-activated protein kinase MEK kinase, the Janus kinases, or the receptor tyrosine kinase epidermal growth factor receptor or platelet-derived growth factor receptor. Taken together, our results suggest an essential role for BLT1 endocytosis and Yes kinase activation in LTB4-mediated degranulation of human neutrophils.

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G Protein-coupled Receptors Mediate Two Functionally Distinct Pathways of Tyrosine Phosphorylation in Rat 1a Fibroblasts

Cited by 194 publications

References 48 publications

SH3 Binding Domains in the Dopamine D4 Receptor

SH3 Binding Domains in the Dopamine D4 Receptor

AKAPs (A-kinase anchoring proteins) and molecules that compose their G-protein-coupled receptor signalling complexes

Involvement of BLT1 Endocytosis and Yes Kinase Activation in Leukotriene B4-Induced Neutrophil Degranulation

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