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Rac1b, A Variant Of Rac1 Interacts With Calmodulin
Author(s) -
Khaneha,
Xu Bing,
Chelikani Prashen,
Bhullar Rajinder Pal
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1046.7
Subject(s) - calmodulin , gtp' , rac1 , gtpase , effector , gene isoform , amino acid , function (biology) , chemistry , microbiology and biotechnology , biochemistry , biology , signal transduction , gene , enzyme
Rac1b, a splice isoform of Rac1, is up‐regulated in malignant colorectal and breast cancer. It contains an additional 19 amino acid insertion close to the switch II domain, a region important for Rac1 interaction with regulators and effectors. This insertion leads to decreased GTPase activity and reduced affinity for GDP, resulting in intracellular predominance of GTP‐bound Rac1b. Previously, a 14 amino acid region essential for calmodulin (CaM) binding has been established in Rac1. A similar region exists in Rac1b. This led to our hypothesis that Rac1b interacts with CaM. Western Blot analysis showed that endogenous Rac1b interacts with CaM‐Sepharose, and that Rac1b binds to pure CaM, in a calcium dependent manner. Experiments using W7, a potent CaM antagonist, revealed that W7 does not play a role in GDP/GTP binding to Rac1b. However, the role of CaM in the activation and function of Rac1b still remains to be analyzed and is being pursued.