A Musical Metaphor for Matrix Function

Plasmamembrane

Plasmamembrane

Cytoplasm

More complex signals organized both in space in the cell (e.g., focal complexes, contacts and adhesions)

and in relation to the surroundings (biological context).

S S

Integrin-Growth Factor Receptor Crosstalk

•Lössner D, et al., Integrin v3mediates upregulation of epidermal growth-factor receptor expression and activity in human ovarian cancer cells, Int J Biochem Cell Biol (2008), doi:10.1016/j.biocel.2008.05.014

•Lee, et al., Integrin Regulation by Vascular Endothelial Growth Factor in Human Brain Microvascular Endothelial Cells, The Journal of Biological Chemistry Vol. 281, no. 52, pp. 40450–40460, December 29, 2006

EGFR upregulation leads to increased proliferation

Northern

Integrin-Growth Factor Receptor Crosstalk

Shu-Yi Chen and Hong-Chen Chen, Direct Interaction of Focal Adhesion Kinase (FAK) with Met Is Required for FAK To Promote Hepatocyte Growth Factor-Induced Cell Invasion, Molecular and Cellular Biology, July 2006, p. 5155–5167

Integrin-Growth Factor Receptor Crosstalk

Short et.al., Integrin-mediated Signaling Events in Human Endothelial Cells, Molecular Biology of the Cell Vol. 9, 1969–1980, August 1998

Integrin-Growth Factor Receptor Crosstalk

•Borges et al., Platelet-derived Growth Factor Receptor and Vascular Endothelial Growth Factor Receptor 2 Bind to the 3 Integrin through Its Extracellular Domain The Journal of Biological Chemistry Vol. 275, No. 51, Issue of December 22, pp. 39867–39873, 2000

•Zhang et. al., Extracellular Matrix Regulates Endothelial Functions Through Interaction of VEGFR-3 and Integrin 51 Journal of Cellular Physiology 202:205–214 (2005)

•Mahabeleshwar et.al., Mechanisms of Integrin Vascular Endothelial Growth Factor Receptor Cross-Activation in Angiogenesis Circ. Res. 2007;101;570-580

•Moro et. al., Integrins induce activation of EGF receptor: role in MAP kinase induction and adhesion-dependent cell survival, The EMBO Journal Vol.17 No.22 pp.6622–6632, 1998

Interaction independent of ligand

Cytoplasmic tail not neededExtracellular domain mediates interaction

Src phosphorylates 3

Src phosphorylation determines 3 activity

3 cytoplasmic tyrosine motifs are required for v3-dependent migration of ECs and EC tube formation

Blocking antibodies

Effects on PI3K acivity