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First published online May 20, 2009

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The pathway of lumenogenesis

During vascular morphogenesis, the formation of the endothelial-cell (EC) lumen is controlled by a complex network of signalling pathways. George Davis and colleagues previously showed that essential signalling molecules in this pathway include protein kinase C (PKC), Rho GTPases, and the downstream kinases Pak2 and Pak4. On page 1812, the same group now investigates in greater detail the signalling pathways that underlie the formation of the EC lumen in three-dimensional collagen matrix assays. They show for the first time that the Src-family nonreceptor tyrosine kinases (SFKs) Src and Yes – which regulate the actin cytoskeleton and cell migration – are also involved in EC lumen formation. They also confirm the requirement for PKC activation in this process, which is shown to trigger the activation of SFKs. SFKs regulate the activation of Rho GTPases in many cellular processes; here, the authors report that a multiprotein complex containing SFKs directly associates with the Rho GTPase Cdc42 during EC lumen formation. In addition, PKC is required for this interaction. PKC and Cdc42 trigger a downstream kinase cascade by activating Pak2 and Pak4, which activate B-Raf and C-Raf, followed by ERK1 and ERK2 activation. As each kinase in this pathway is essential, these results define a linear signalling pathway that is required for the formation of the EC lumen.

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Formation of endothelial lumens requires a coordinated PKC-, Src-, Pak- and Raf-kinase-dependent signaling cascade downstream of Cdc42 activation

Wonshill Koh, Kamakshi Sachidanandam, Amber N. Stratman, Anastasia Sacharidou, Anne M. Mayo, Eric A. Murphy, David A. Cheresh, and George E. Davis
JCS 2009 122: 1812-1822. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?