Coupling receptor tyrosine kinases to Rho GTPases--GEFs what's the link

Document Type

Article

Publication Date

11-2006

Publication Title

Cellular Signalling

Volume

18

Issue

11

First page number:

1834

Last page number:

1843

Abstract

Rho GTPases are molecular switches involved in the regulation of many cellular processes. This review summarizes work examining how stimulation of receptor tyrosine kinases (RTKs) leads to the activation of Rho guanine nucleotide exchange factors (GEFs) and their Rho GTPase substrates. The collective findings strongly suggest that RTK signaling to Rho proteins is a general signal transduction mechanism, like RTK mediated activation of phosphatidyl inositol 3-kinase, phospholipase Cgamma, and the mitogen activated protein kinase (MAPK) pathway. More than half of the 58 known human RTKs activate at least one Rho family member. Likewise, 16 Rho GEFs directly interact with and/or are phosphorylated by a RTK. The specificity of receptor tyrosine kinase/Rho GEF signaling seems to be somewhat promiscuous. There several cases where multiple RTKs activate the same Rho GEF and where a single RTK can activate multiple Rho GEFs. Expression analysis indicates that the average human tissue contains transcripts for 33 RTKs, 34 Rho GEFs, and 14 Rho GTPases with each tissue containing a unique complement of these proteins. Given the promiscuity of RTKs for Rho GEFs, Rho GEFs for Rho GTPases, and the large number of these proteins expressed in cells, a complex combinatorial network of proteins in these families may contribute to coding specific signals and cell responses from RTKs.

Keywords

Cellular signal transduction; Guanine Nucleotide Exchange Factors/metabolism; Humans; Men; Pleckstrin homology domain; Receptor Protein-Tyrosine Kinases/metabolism; Receptor tyrosine kinase; Rho; Rho GEF; Rho GTPases; rho GTP-Binding Proteins/metabolism; Signal Transduction; Women

Disciplines

Life Sciences | Molecular Biology | Neurosciences | Structural Biology

Language

English

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