Related Experiment Video

Updated: Aug 9, 2026

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells
08:54

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells

Published on: July 20, 2014

Csk-binding protein (Cbp) negatively regulates epidermal growth factor-induced cell transformation by controlling Src

L Q Jiang1, X Feng, W Zhou

  • 1Key Laboratory of Proteomics, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

Oncogene
|April 26, 2006
PubMed

Insights

Csk-binding protein (Cbp) negatively regulates cell transformation and tumor growth by suppressing Src activation. This study reveals Cbp

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Cancer Research

Background:

  • Epidermal growth factor receptor (EGFR) and Src tyrosine kinase are key regulators of cell signaling, transformation, and tumorigenesis.
  • Src activation is controlled by C-terminal Src kinase (Csk), and Csk-binding protein (Cbp) is known to suppress T-cell receptor activation.
  • The role of Cbp in epidermal growth factor (EGF)-induced cellular activities remained largely unexplored.

Purpose of the Study:

  • To investigate the function of Csk-binding protein (Cbp) in epidermal growth factor (EGF)-mediated signaling pathways.
  • To determine Cbp's role in regulating Src activation, cell transformation, and tumor cell growth.
  • To explore Cbp's involvement in receptor tyrosine kinase (RTK)-activated signaling.

Main Methods:

  • Investigated EGF-stimulation-induced Cbp tyrosine phosphorylation and its association with Csk.
  • Utilized expression of wild-type (wt) Cbp and a mutant form (CbpY317F) to assess effects on Src, ERK1/2, and Akt-1 activation.
  • Employed RNA interference (RNAi) to knockdown endogenous Cbp in NIH3T3 cells and evaluated cell transformation and soft agar colony formation in cancer cell lines.

Main Results:

  • EGF stimulation induced Cbp tyrosine phosphorylation and Cbp-Csk association in a Src family kinase (SFK)-dependent manner.
  • Overexpression of wt Cbp suppressed EGF-induced activation of Src, ERK1/2, Akt-1, NIH3T3 cell transformation, and MDA-MB-468 colony formation.
  • Expression of CbpY317F or Cbp knockdown enhanced EGF-induced signaling and cell transformation, indicating Cbp's inhibitory role.

Conclusions:

  • Csk-binding protein (Cbp) acts as a negative regulator of cell transformation and tumor cell growth by downregulating Src activation.
  • Cbp plays a significant role in modulating EGF-induced signaling pathways.
  • Cbp may be broadly involved in receptor tyrosine kinase (RTK)-activated signaling and tumorigenesis.

More Related Videos

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Related Concept Videos

Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
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...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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...