Related Experiment Video

Updated: Jun 24, 2026

Spatial and Temporal Analysis of Active ERK in the C. elegans Germline
08:40

Spatial and Temporal Analysis of Active ERK in the C. elegans Germline

Published on: November 29, 2016

Erbin and the NF2 tumor suppressor Merlin cooperatively regulate cell-type-specific activation of PAK2 by TGF-beta

Mark C Wilkes1, Claire E Repellin, Min Hong

  • 1Thoracic Diseases Research Unit, Department of Biochemistry and Molecular Biology and Mayo Clinic Cancer Center, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.

Developmental Cell
|March 18, 2009
PubMed

Insights

Erbin protein prevents inappropriate PAK2 activation in epithelial cells, controlling TGF-beta signaling. This discovery highlights Erbin

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Transforming growth factor beta (TGF-beta) ligands have diverse effects on cell growth and differentiation.
  • PAK2 activation is crucial for TGF-beta's action in mesenchymal cells but not epithelial cells.

Purpose of the Study:

  • To investigate the regulatory mechanisms preventing inappropriate PAK2 activation in epithelial cells.
  • To understand how Erbin influences TGF-beta signaling and Merlin function in different cell types.

Main Methods:

  • Investigated protein interactions and cellular signaling pathways.
  • Utilized epithelial cell cultures to study regulatory constraints.

Main Results:

  • Erbin, an epithelial-enriched protein, controls the NF2 tumor suppressor Merlin's function.
  • Erbin dictates Merlin's interaction with active PAK2.
  • Erbin/Merlin complexes inactivate PAK2 in epithelial cells, conferring resistance to TGF-beta.
  • Mesenchymal cells lacking Erbin show TGF-beta-induced inhibition of Merlin function via PAK2.

Conclusions:

  • Erbin is a key factor in epithelial cells' resistance to TGF-beta signaling.
  • Erbin regulates Merlin tumor suppressor activity by modulating PAK2 binding and function.

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
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...
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...
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.
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...
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...