Regulation of tyrosine kinase cascades by G-protein-coupled receptors

Luttrell, Louis M.; Daaka, Yehia; Lefkowitz, Robert J.

doi:10.1016/s0955-0674(99)80023-4

Cited by 636 publications

(450 citation statements)

References 55 publications

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“…It has been known for a quite long time that receptors can functionally interact by sharing signaling pathways or by mechanisms of transactivation (Luttrel et al, 1999;Köse, 2017). This formally fits the definition of RRI in a functional sense, although the involved proteins may never physically come into contact with each other (see Prezeau et al, 2010, for a detailed analysis).…”

Section: Rri As Allosteric Interactionsmentioning

confidence: 62%

G protein-coupled receptor-receptor interactions give integrative dynamics to intercellular communication

Guidolin

Marcoli

Tortorella

et al. 2018

Reviews in the Neurosciences

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Abstract:The proposal of receptor-receptor interactions (RRIs) in the early 1980s broadened the view on the role of G protein-coupled receptors (GPCR) in the dynamics of the intercellular communication. RRIs, indeed, allow GPCR to operate not only as monomers but also as receptor complexes, in which the integration of the incoming signals depends on the number, spatial arrangement, and order of activation of the protomers forming the complex. The main biochemical mechanisms controlling the functional interplay of GPCR in the receptor complexes are direct allosteric interactions between protomer domains. The formation of these macromolecular assemblies has several physiologic implications in terms of the modulation of the signaling pathways and interaction with other membrane proteins. It also impacts on the emerging field of connectomics, as it contributes to set and tune the synaptic strength. Furthermore, recent evidence suggests that the transfer of GPCR and GPCR complexes between cells via the exosome pathway could enable the target cells to recognize/decode transmitters and/or modulators for which they did not express the pertinent receptors. Thus, this process may also open the possibility of a new type of redeployment of neural circuits. The fundamental aspects of GPCR complex formation and function are the focus of the present review article.

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Section: Rri As Allosteric Interactionsmentioning

confidence: 62%

G protein-coupled receptor-receptor interactions give integrative dynamics to intercellular communication

Guidolin

Marcoli

Tortorella

et al. 2018

Reviews in the Neurosciences

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“…Ligation of HGF to the extracellular domain of c-Met results in receptor dimerization, phosphorylation of multiple tyrosine residues at the intracellular region, and binding and activation of signal transducers such as PI-3-Kinase, PLC, STATs, and Erk1/2 [22,[25][26][27]. Transactivation of RTKs by GPCRs induces tyrosine phosphorylation of RTKs and hence results in further signal transduction [5][6][7][8][9]. We have shown that LPA induced tyrosine phosphorylation of EGF-R and PDGF-Rβ in HBEpCs [20,21].…”

Section: Discussionmentioning

confidence: 99%

“…These include G-protein-coupled receptors (GPCRs), receptor tyrosine kinases (RTKs), cytokine receptor-activated kinases, and members of the steroid/ thyroid hormone receptor super family [1][2][3]. Originally, these receptors were thought to act independently, but in recent years evidence of cross-talk between these different classes of receptors has been discovered [4][5][6][7][8][9]. Among them, the cross-talk between GPCRs and RTKs has been most frequently identified [5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

“…Originally, these receptors were thought to act independently, but in recent years evidence of cross-talk between these different classes of receptors has been discovered [4][5][6][7][8][9]. Among them, the cross-talk between GPCRs and RTKs has been most frequently identified [5][6][7][8][9]. Activation of GPCRs leads to stimulation of RTKs, providing integration and amplification of signaling pathways that regulate cellular responses and functions [5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

“…Among them, the cross-talk between GPCRs and RTKs has been most frequently identified [5][6][7][8][9]. Activation of GPCRs leads to stimulation of RTKs, providing integration and amplification of signaling pathways that regulate cellular responses and functions [5][6][7][8][9]. In contrast to transactivation of RTKs by GPCRs, increasing evidence shows that GPCRs also induce inhibition of RTK activity, known as transinactivation [10][11].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Lysophosphatidic acid modulates c-Met redistribution and hepatocyte growth factor/c-Met signaling in human bronchial epithelial cells through PKC δ and E-cadherin

Zhao¹,

He²,

Stern³

et al. 2007

Cellular Signalling

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Previously we demonstrated that ligation of lysophosphatidic acid (LPA) to G protein-coupled LPA receptors induces transactivation of receptor tyrosine kinases (RTKs), such as platelet-derived growth factor receptor beta (PDGF-Rβ) and epidermal growth factor receptor (EGF-R), in primary cultures of human bronchial epithelial cells (HBEpCs). Here we examined the role of LPA on c-Met redistribution and modulation of hepatocyte growth factor ( These results demonstrate that LPA regulates c-Met function through PKC δ-and E-cadherin in HBEpCs, suggesting an alternate function of the cross-talk between G-protein coupled receptors (GPCRs) and RTKs in HBEpCs.

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Genetic Information, Genomic Technologies, and the Future of Drug Discovery

Bumol

Watanabe²

2001

JAMA

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The completion of the first draft of the human genome has provided an unprecedented opportunity to understand the genetic and molecular basis of disease. Parallel developments of new biological technologies, such as transcript profiling, allow scientists to examine almost any biological system in high molecular resolution. Contemporary drug discovery research is now focusing on the identification and validation of pharmaceutical targets in the molecular pathways/systems embedded in this information. Novel therapeutic interventions are being developed and evaluated as a result of this research which will be the basis of innovative pharmaceuticals of the future.

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Regulation of tyrosine kinase cascades by G-protein-coupled receptors

Cited by 636 publications

References 55 publications

G protein-coupled receptor-receptor interactions give integrative dynamics to intercellular communication

G protein-coupled receptor-receptor interactions give integrative dynamics to intercellular communication

Lysophosphatidic acid modulates c-Met redistribution and hepatocyte growth factor/c-Met signaling in human bronchial epithelial cells through PKC δ and E-cadherin

Genetic Information, Genomic Technologies, and the Future of Drug Discovery

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