Related Experiment Video

Updated: Aug 9, 2026

Rapid and Robust Analysis of Cellular and Molecular Polarization Induced by Chemokine Signaling
10:03

Rapid and Robust Analysis of Cellular and Molecular Polarization Induced by Chemokine Signaling

Published on: December 12, 2014

Differential effects of Cbl and 70Z/3 Cbl on T cell receptor-induced phospholipase Cgamma-1 activity

L J Graham1, K E DeBell, M Verí

  • 1Laboratory of Immunobiology, Division of Monoclonal Antibodies, Center for Biologics Evaluation and Research, HFM-564, Building 29B, Room 3NN10, 29 Lincoln Drive MSC 4555, Bethesda, MD 20892-4555, USA.

FEBS Letters
|April 4, 2000
PubMed

Insights

Cbl and oncogenic 70Z/3 Cbl proteins differentially regulate phospholipase Cgamma1 (PLCgamma1) activation, impacting calcium signaling pathways. This study clarifies their opposing roles in T cell receptor signaling.

Area of Science:

  • Cellular signaling
  • Immunology
  • Molecular biology

Background:

  • Cbl proteins are key regulators of signal transduction pathways.
  • Oncogenic Cbl variants can alter normal cellular processes.
  • Phospholipase Cgamma1 (PLCgamma1) activation is crucial for T cell receptor signaling.

Purpose of the Study:

  • To investigate the differential effects of Cbl and oncogenic 70Z/3 Cbl on PLCgamma1 activation.
  • To elucidate the role of Cbl proteins in regulating inositol phospholipid (PI) hydrolysis.
  • To understand the impact on calcium/Ras-sensitive NF-AT reporter activity.

Main Methods:

  • Analysis of NF-AT reporter construct activation.
  • Measurement of PLCgamma1-mediated inositol phospholipid (PI) hydrolysis.
  • Assessment of PLCgamma1 tyrosine phosphorylation.

Main Results:

  • Cbl overexpression reduced T cell receptor-induced PI hydrolysis without affecting PLCgamma1 phosphorylation.
  • 70Z/3 Cbl expression increased basal and OKT3-induced PLCgamma1 phosphorylation and PI hydrolysis.
  • Differential regulation of PLCgamma1 phosphorylation and activation by Cbl and 70Z/3 Cbl was observed.

Conclusions:

  • Cbl and 70Z/3 Cbl exhibit opposing effects on PLCgamma1 activation.
  • These differential effects contribute to the distinct regulation of calcium/Ras-sensitive NF-AT reporters.
  • The findings provide insights into Cbl-mediated signaling regulation mechanisms.

More Related Videos

Rapid Quantification of Mitogen-induced Blastogenesis in T Lymphocytes for Identifying Immunomodulatory Drugs08:13

Rapid Quantification of Mitogen-induced Blastogenesis in T Lymphocytes for Identifying Immunomodulatory Drugs

Published on: December 27, 2016

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

Related Concept Videos

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 Second Messengers01:15

Amplifying Signals via Second Messengers

Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
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...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...