Related Experiment Video

Updated: Aug 13, 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

An oncogenic epidermal growth factor receptor signals via a p21-activated kinase-caldesmon-myosin phosphotyrosine

M J McManus1, J L Boerner, A J Danielsen

  • 1Department of Biochemistry and Molecular Biology and the Tumor Biology Program, Mayo Clinic, Rochester, Minnesota 55905, USA.

The Journal of Biological Chemistry
|August 24, 2000
PubMed

Insights

Constitutively activated epidermal growth factor receptor (EGFR) mutants form a unique signaling module with myosin II, driving cell transformation. This pathway, distinct from normal growth signals, involves Rho-dependent tyrosine phosphorylation of p21-activated kinase (Pak).

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Biochemistry

Background:

  • Ligand-independent receptor tyrosine kinases (RTKs) can drive tumor formation.
  • The specific signaling pathways mediating this oncogenic transformation are not fully understood.

Purpose of the Study:

  • To investigate the biochemical signals involved in ligand-independent cellular transformation by a constitutively active epidermal growth factor receptor (EGFR) mutant (v-ErbB).
  • To identify the molecular components and regulatory mechanisms of this transformation-specific signaling.

Main Methods:

  • Analysis of signaling complexes formed by v-ErbB in transformed cells.
  • Identification of protein-protein interactions and post-translational modifications (tyrosine phosphorylation).
  • Investigation of small GTPase dependency (Rho, Ras, Rac, Cdc42) for signaling events.

Main Results:

  • v-ErbB forms a novel signaling module involving signal adapter proteins (Shc, Grb2, Nck) and myosin II.
  • This module includes tyrosine-phosphorylated p21-activated kinase (Pak), caldesmon, and myosin light chain kinase.
  • Rho-dependent tyrosine phosphorylation of Pak enhances its kinase activity, distinct from canonical mitogenic pathways.

Conclusions:

  • Ligand-independent EGFR mutants activate distinct oncogenic signaling pathways separate from growth factor-dependent mitogenic signals.
  • A myosin-associated signaling module couples oncogenic RTKs to the actomyosin cytoskeleton.
  • This module may regulate cellular mechanics, contributing to anchorage-independent growth and tumorigenesis.

More Related Videos

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation15:05

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

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...
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...
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...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
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...