Related Experiment Video

Updated: Oct 21, 2026

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
07:42

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays

Published on: September 19, 2018

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

L M Luttrell1, Y Daaka, R J Lefkowitz

  • 1The Howard Hughes Medical Institute, Departments of Medicine, Surgery and Biochemistry, Box 3821, Duke University Medical Center, Durham, NC 27710, USA.

Current Opinion in Cell Biology
|April 21, 1999
PubMed

Insights

G-protein-coupled receptors (GPCRs) utilize tyrosine kinases to assemble signaling complexes on scaffolds like receptor tyrosine kinases (RTKs) and focal adhesions. GPCR desensitization also impacts this signaling pathway.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Biochemistry

Background:

  • G-protein-coupled receptors (GPCRs) mediate crucial cellular responses.
  • Mitogenic signaling involves tyrosine phosphorylation and assembly of Ras activation complexes.
  • Recent research has identified novel scaffolds for GPCR-directed complex assembly.

Purpose of the Study:

  • To elucidate the mechanisms of mitogenic signaling initiated by GPCRs.
  • To identify and characterize the scaffolds involved in GPCR-mediated Ras activation.
  • To understand the role of nonreceptor tyrosine kinases and GPCR desensitization in these pathways.

Main Methods:

  • Investigated tyrosine phosphorylation of adaptor proteins.
  • Analyzed the assembly of multiprotein Ras activation complexes.
  • Examined the involvement of receptor tyrosine kinases (RTKs), focal adhesions, and GPCRs as scaffolds.
  • Studied the role of nonreceptor tyrosine kinases.
  • Assessed the impact of GPCR desensitization and clathrin-coated pit sequestration.

Main Results:

  • Identified three distinct scaffolds for GPCR-directed complex assembly: transactivated RTKs, integrin-based focal adhesions, and GPCRs.
  • Demonstrated the critical role of nonreceptor tyrosine kinases in all identified scaffold systems.
  • Showed that GPCR desensitization and sequestration via clathrin-coated pits influence signaling through RTK- and GPCR-based scaffolds.

Conclusions:

  • Mitogenic signaling by GPCRs is a complex process involving multiple scaffolds and tyrosine kinases.
  • Scaffold identification provides new insights into the regulation of Ras signaling.
  • GPCR desensitization mechanisms are integrated with scaffold-dependent signaling pathways.

More Related Videos

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes09:40

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes

Published on: September 28, 2018

Development and Application of Rapamycin-regulated Tyrosine Phosphatases06:56

Development and Application of Rapamycin-regulated Tyrosine Phosphatases

Published on: September 6, 2024

Related Concept Videos

Enzyme-linked Receptors01:13

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Enzyme-linked Receptors01:13

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include: