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Matrix survival signaling: from fibronectin via focal adhesion kinase to c-Jun NH(2)-terminal kinase

E A Almeida1, D Ilić, Q Han

  • 1Department of Stomatology and Department of Anatomy, Department of Medicine, University of California San Francisco, San Francisco, California 94143-0512, USA.

The Journal of Cell Biology
|May 3, 2000
PubMed

Insights

Fibroblast survival depends on distinct pathways initiated by fibronectin or serum. Fibronectin signals through focal adhesion kinase (FAK) and c-Jun NH2-terminal kinase (JNK), while serum uses FAK, phosphatidylinositol 3-kinase (PI3K), and Akt.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Transformed cells often lose dependence on anchorage and serum for survival.
  • Fibronectin signaling via focal adhesion kinase (FAK) suppresses apoptosis in the absence of serum.
  • Previous work identified FAK-mediated survival signals in primary fibroblasts and endothelial cells.

Purpose of the Study:

  • Identify survival sequences within FAK.
  • Determine signaling molecules downstream of FAK crucial for anchorage-dependent survival.
  • Investigate distinct survival pathways mediated by extracellular matrix and serum.

Main Methods:

  • Utilized primary fibroblasts cultured on fibronectin or collagen.
  • Investigated protein interactions using techniques like SH3 domain binding assays.
  • Analyzed signaling pathways including FAK, p130Cas, JNK, Ras/Rac1/Pak1/MKK4, PI3-kinase, and Akt/PKB.

Main Results:

  • Binding of p130Cas SH3 domain to FAK is essential for fibroblast survival on fibronectin without serum.
  • The FAK-p130Cas complex activates c-Jun NH2-terminal kinase (JNK) through a Ras/Rac1/Pak1/MKK4 pathway.
  • Activated JNK localizes with FAK in focal adhesions on fibronectin, promoting survival, unlike on collagen.
  • Serum-dependent survival involves FAK, PI3-kinase, and Akt/PKB, distinct from the fibronectin-FAK-JNK pathway when serum is absent.

Conclusions:

  • Fibronectin-mediated survival in serum-deprived conditions relies on the FAK-p130Cas-JNK axis.
  • Serum-dependent survival utilizes a separate FAK-PI3-kinase-Akt pathway.
  • FAK acts as a central transducer for distinct extracellular matrix and serum survival signals.

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