Activation of Rac1 by Rho-guanine nucleotide dissociation inhibitor-beta with defective isoprenyl-binding pocket

作者：Ota Takahide^*; Maeda Masayo; Murakami Manabu; Takegami Tsutomu; Suto Shiho; Tatsuka Masaaki

来源：Cell Biology International, 2007, 31(1): 92-96.

DOI：10.1016/j.cellbi.2006.09.002

• RhoGDI
• Rac1
• prenylation
• metastasis

Rho-guanine nucleotide dissociation inhibitor-P (RhoGDI beta), a regulator for Rho GTPases, is implicated in cancer cell progression. We reported that C-terminal truncated RhoGDI beta (Delta C(166-201)-RhoGD beta) promoted metastasis through activating Rac1 signaling pathway in ras-transformed fibroblast cells. To better understand the mechanism of Rac1 activation by Delta C(166-201)-RhoGDI beta during metastasis, the amount of GTP-bound Rac1 was measured as the activation level of Rac1 in cells expressing various mutant RhoGDI beta with sequential C-terminal deletions. Three C-terminal hydrophobic amino acid residues (Trp191, Leu193, and Ile195) supposed to interact with isoprenyl groups of Rac1, was indispensable for a proper regulation of Rac1 activation/inhibition. Deletion of this region led RhoGDI beta to continuously associate with GTP-bound Rac1, provoking constitutive activation of Rac1. Thus, impaired interaction of RhoGDI beta with Rac1 isoprenyl groups possibly makes RhoGDI beta function as a positive regulator for Rac1 during metastasis.

• 出版日期2007-1
• 单位河北医科大学