Activation of a signaling cascade by cytoskeleton stretch

Masako Tamada, Michael Sheetz, Yasuhiro Sawada

Research output: Contribution to journalArticle

215 Citations (Scopus)

Abstract

Cells sense and respond to mechanical force. However, the mechanisms of transduction of extracellular matrix (ECM) forces to biochemical signals are not known. After removing the cell membrane and soluble proteins by Triton X-100 extraction, we found that the remaining complex (Triton cytoskeletons) activated Rap1 upon stretch. Rap1 guanine nucleotide exchange factor, C3G, was required for this activation; C3G as well as the adaptor protein, CrkII, in cell extract bound to Triton cytoskeletons in a stretch-dependent manner. CrkII binding, which was Cas dependent, correlated with stretch-dependent tyrosine phosphorylation of proteins in Triton cytoskeletons including Cas at the contacts with ECM. These in vitro findings were compatible with in vivo observations of stretch-enhanced phosphotyrosine signals, accumulation of CrkII at cell-ECM contacts, and CrkII-Cas colocalization. We suggest that mechanical force on Triton cytoskeletons activates local tyrosine phosphorylation, which provides docking sites for cytosolic proteins, and initiates signaling to activate Rap1.

Original languageEnglish (US)
Pages (from-to)709-718
Number of pages10
JournalDevelopmental Cell
Volume7
Issue number5
DOIs
StatePublished - Nov 1 2004
Externally publishedYes

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Cytoskeleton
Chemical activation
Extracellular Matrix
Phosphorylation
Guanine Nucleotide-Releasing Factor 2
Tyrosine
Proteins
Phosphotyrosine
Octoxynol
Cell membranes
Cell Extracts
Membrane Proteins

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Activation of a signaling cascade by cytoskeleton stretch. / Tamada, Masako; Sheetz, Michael; Sawada, Yasuhiro.

In: Developmental Cell, Vol. 7, No. 5, 01.11.2004, p. 709-718.

Research output: Contribution to journalArticle

Tamada, Masako ; Sheetz, Michael ; Sawada, Yasuhiro. / Activation of a signaling cascade by cytoskeleton stretch. In: Developmental Cell. 2004 ; Vol. 7, No. 5. pp. 709-718.
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