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Related Concept Videos

Cell Migration01:09

Cell Migration

Cell migration, the process by which cells move from one location to another, is essential for the proper development and viability of organisms throughout their life. When cells are not able to migrate properly to their ordained locations, various disorders may occur. For example, disruption in cell migration causes chronic inflammatory diseases such as arthritis.
Cell Migration01:19

Cell Migration

Cell migration is a process by which the cells move from one location to another, playing an essential role in embryological development, repair and regeneration, immune response, and metastasis. Cells migrate in response to chemical or mechanical signals generated by specific organs or tissues. The overall mechanism includes three steps - polarization, protrusion, and release. Polarization involves the formation of a distinct cell front and rear, which determines the direction of movement.
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...
Integrins01:10

Integrins

Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
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Activation of Integrins01:15

Activation of Integrins

Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...

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Related Experiment Video

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In vitro Cell Migration and Invasion Assays
09:55

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Published on: June 1, 2014

alpha 2 integrin subunit cytoplasmic domain-dependent cellular migration requires p38 MAPK.

P A Klekotka1, S A Santoro, M M Zutter

  • 1Washington University School of Medicine, St. Louis, Missouri 63110, USA.

The Journal of Biological Chemistry
|December 31, 2000
PubMed
Summary

The alpha(2) integrin cytoplasmic domain uniquely drives cell migration on collagen via the p38 MAP kinase pathway. This pathway is crucial for both epidermal growth factor (EGF)-stimulated and unstimulated cell movement.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Integrins are crucial cell surface receptors mediating cell adhesion and migration.
  • The alpha(2) integrin subunit plays a role in cell interactions with collagenous matrices.
  • Epidermal growth factor (EGF) can stimulate cell migration through various signaling pathways.

Purpose of the Study:

  • To investigate the specific role of the alpha(2) integrin subunit cytoplasmic domain in cell migration.
  • To elucidate the signaling pathways involved in alpha(2) integrin-mediated cell migration on type I collagen.
  • To determine the contribution of the p38 MAP kinase pathway to EGF-stimulated and unstimulated migration.

Main Methods:

  • Utilized cell adhesion assays on collagenous matrices.
  • Employed specific kinase inhibitors (p38 MAP kinase, phosphatidylinositol 3-kinase, MEK).
  • Expressed full-length and chimeric alpha(2) integrin subunits, dominant-negative p38 MAP kinase, and constitutively active Rac1(Val-12).
  • Assessed protein phosphorylation (p38 MAP kinase) and cell migration rates.

Main Results:

  • The alpha(2) integrin cytoplasmic domain uniquely supported EGF-stimulated migration on type I collagen.
  • Inhibitors of p38 MAP kinase and phosphatidylinositol 3-kinase blocked migration, while MEK inhibitors did not.
  • Cells with the full-length alpha(2) subunit showed sustained p38 MAP kinase phosphorylation after collagen adhesion.
  • Dominant-negative p38 MAP kinase expression inhibited migration, and active Rac1 rescued p38 MAP kinase activation and migration in cells with a chimeric alpha(2) subunit.

Conclusions:

  • The alpha(2) integrin cytoplasmic domain uniquely activates the p38 MAP kinase pathway.
  • This pathway is essential for both unstimulated and EGF-stimulated cell migration on type I collagen.
  • Rac1 signaling is linked to p38 MAP kinase activation and migration mediated by the alpha(2) integrin cytoplasmic domain.