Premium
Comparative functional analysis of the Rac GTPases
Author(s) -
Haeusler Lars Christian,
Blumenstein Lars,
Stege Patricia,
Dvorsky Radovan,
Ahmadian Mohammad Reza
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)01351-6
Subject(s) - gtpase , cdc42 , rac gtp binding proteins , guanine nucleotide exchange factor , microbiology and biotechnology , rac1 , pak1 , nucleotide , cytoskeleton , effector , actin cytoskeleton , biology , gene isoform , actin , chemistry , computational biology , biochemistry , phosphorylation , cell , signal transduction , gene
Small GTPases of the Rho family including Rac, Rho and Cdc42 regulate different cellular processes like reorganization of the actin cytoskeleton by acting as molecular switches. The three distinct mammalian Rac proteins share very high sequence identity but how their specificity is achieved is hitherto unknown. Here we show that Rac1 and Rac3 are very closely related concerning their biochemical properties, such as effector interaction, nucleotide binding and hydrolysis. In contrast, Rac2 displays a slower nucleotide association and is more efficiently activated by the Rac‐GEF Tiam1. Modeling and normal mode analysis support the idea that altered dynamics of Rac2 at the switch I region may be responsible for different biochemical properties. These results provide insight into the individual functionalities of the Rac isoforms.