Related Experiment Video

Updated: May 15, 2026

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration
10:43

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration

Published on: May 19, 2016

The MLK-related kinase (MRK) is a novel RhoC effector that mediates lysophosphatidic acid (LPA)-stimulated tumor cell

Olga Korkina1, Zhiwan Dong, Allison Marullo

  • 1Oncology and Cell Biology Center, The Feinstein Institute for Medical Research, Manhasset, New York 11030, USA.

The Journal of Biological Chemistry
|January 16, 2013
PubMed

Insights

The MAP3K protein MRK acts as a novel RhoC effector, regulating cell invasion by controlling myosin dynamics and MAP kinases like ERK and p38. Depleting MRK mimics RhoC depletion, inhibiting invasion.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • The small GTPase RhoC is crucial for tumor metastasis and its functions differ from the highly homologous RhoA.
  • Signaling pathways differentially regulated by RhoA and RhoC are not fully understood.

Purpose of the Study:

  • To identify signaling components differentially regulated by RhoA and RhoC.
  • To investigate the role of the MAP3K protein MRK in Rho GTPase-mediated cell invasion.

Main Methods:

  • In vitro binding assays to test MRK interaction with RhoA and RhoC.
  • siRNA-mediated gene depletion to assess the cellular functions of MRK, RhoA, and RhoC.
  • Analysis of LPA-stimulated cell invasion and myosin light chain phosphorylation.
  • Assessment of p38 and ERK MAP kinase activation.

Main Results:

  • MRK directly binds to GTP-bound RhoA and RhoC.
  • MRK depletion phenocopies RhoC depletion, inhibiting LPA-stimulated invasion, whereas RhoA depletion increases invasion.
  • MRK regulates myosin light chain phosphorylation and is required for LPA-induced activation of p38 and ERK MAP kinases.

Conclusions:

  • MRK is identified as a novel RhoC effector.
  • MRK plays a critical role in regulating LPA-stimulated cell invasion through modulation of myosin dynamics and MAP kinase pathways (ERK and p38).

More Related Videos

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis08:55

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis

Published on: August 7, 2018

Related Concept Videos

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...
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...
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...
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...