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Related Concept Videos

Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
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...
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...
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...
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...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...

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Related Experiment Video

Updated: Jun 5, 2026

Pull-down of Calmodulin-binding Proteins
07:51

Pull-down of Calmodulin-binding Proteins

Published on: January 23, 2012

Calmodulin binds HER2 and modulates HER2 signaling.

Colin D White1, Zhigang Li, David B Sacks

  • 1Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.

Biochimica Et Biophysica Acta
|December 28, 2010
PubMed
Summary

Calmodulin (CaM) binds to two sites on the HER2 protein, influencing breast cancer growth. Inhibiting this interaction may offer a new therapeutic strategy for HER2-positive breast cancers.

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Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
14:20

Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?

Published on: June 13, 2014

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Human epidermal growth factor receptor 2 (HER2) overexpression is linked to poor prognosis in breast cancer.
  • HER2 drives tumorigenesis through protein-protein interactions with signaling molecules.
  • Targeting these interactions presents therapeutic opportunities.

Purpose of the Study:

  • To identify specific binding sites of Calmodulin (CaM) on HER2.
  • To investigate the role of CaM-HER2 interaction in HER2 signaling and cell growth.
  • To evaluate the therapeutic potential of inhibiting CaM-HER2 binding.

Main Methods:

  • Identified CaM binding sites on the N-terminal portion of the HER2 intracellular domain using deletion analysis.
  • Assessed CaM-HER2 binding in a calcium-dependent manner.
  • Measured the impact of CaM inhibition or HER2 binding site deletion on HER2 phosphorylation and cell proliferation.

Main Results:

  • CaM binds to two distinct sites on HER2 (residues 676-689 and 714-732) in a calcium-regulated manner.
  • Deletion of these sites abolished CaM-HER2 interaction.
  • Inhibition of CaM or deletion of binding sites significantly reduced HER2 phosphorylation and HER2-stimulated cell growth.

Conclusions:

  • CaM interacts with HER2 at specific intracellular sites.
  • CaM binding is crucial for HER2 phosphorylation and HER2-driven cell proliferation.
  • Inhibiting the CaM-HER2 interaction is a potential therapeutic strategy for HER2-positive breast cancer.