Related Experiment Video

Updated: May 30, 2026

Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
07:26

Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis

Published on: January 31, 2025

SH3KBP1-binding protein 1 prevents epidermal growth factor receptor degradation by the interruption of c-Cbl-CIN85

Lifeng Feng1, Jin-Tao Wang, Hongchuan Jin

  • 1College of Lifescience, Zhejiang University, Hangzhou, Zhejiang, China.

Cell Biochemistry and Function
|August 11, 2011
PubMed

Insights

SH3KBP1 binding to CIN85 inhibits EGFR degradation by blocking the c-Cbl-CIN85 interaction. This promotes the epidermal growth factor receptor (EGFR) signaling pathway, enhancing transcription activity.

Area of Science:

  • Cellular biology
  • Molecular signaling
  • Protein-protein interactions

Background:

  • Cbl-interacting protein of 85 kDa (CIN85) binding to c-Cbl is crucial for epidermal growth factor receptor (EGFR) endocytosis and degradation.
  • The PXXXPR motif in c-Cbl and SH3 domains of CIN85 mediate this interaction.

Purpose of the Study:

  • To investigate the role of SH3KBP1-binding protein 1 (SHKBP1) in the c-Cbl-CIN85 interaction and its impact on EGFR signaling.

Main Methods:

  • Investigated the binding of SHKBP1 to CIN85 using its PXXXPR motifs.
  • Assessed the effect of SHKBP1 binding on CIN85-c-Cbl interaction.
  • Examined the translocation of CIN85 to EGFR-containing vesicles.
  • Measured EGF-induced serum response element transcription activity.

Main Results:

  • SHKBP1 constitutively binds to the SH3 domains of CIN85.
  • SHKBP1 binding prevents CIN85 from interacting with c-Cbl.
  • SHKBP1 inhibits CIN85 translocation to EGFR-containing vesicles, reducing EGFR degradation.
  • SHKBP1 enhances EGF-induced transcription activity.

Conclusions:

  • SHKBP1 promotes the EGFR signaling pathway by disrupting the c-Cbl-CIN85 complex.
  • Inhibition of EGFR degradation by SHKBP1 leads to enhanced downstream signaling.

More Related Videos

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

Screening and Identification of Small Peptides Targeting Fibroblast Growth Factor Receptor2 using a Phage Display Peptide Library07:32

Screening and Identification of Small Peptides Targeting Fibroblast Growth Factor Receptor2 using a Phage Display Peptide Library

Published on: September 30, 2019

Related Concept Videos

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...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
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...
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...