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Published online
doi:10.1083/jcb.200707022
The Journal of Cell Biology, Vol. 181, No. 3, 537-549
The Rockefeller University Press, 0021-9525 $30.00
© Kakinuma et al.
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Article

Kank regulates RhoA-dependent formation of actin stress fibers and cell migration via 14-3-3 in PI3K–Akt signaling



Naoto Kakinuma, Badal Chandra Roy, Yun Zhu, Yong Wang, and Ryoiti Kiyama

Signaling Molecules Research Laboratory, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8566, Japan

Correspondence to R. Kiyama: kiyama.r{at}aist.go.jp

Phosphoinositide-3 kinase (PI3K)/Akt signaling is activated by growth factors such as insulin and epidermal growth factor (EGF) and regulates several functions such as cell cycling, apoptosis, cell growth, and cell migration. Here, we find that Kank is an Akt substrate located downstream of PI3K and a 14-3-3–binding protein. The interaction between Kank and 14-3-3 is regulated by insulin and EGF and is mediated through phosphorylation of Kank by Akt. In NIH3T3 cells expressing Kank, the amount of actin stress fibers is reduced, and the coexpression of 14-3-3 disrupted this effect. Kank also inhibits insulin-induced cell migration via 14-3-3 binding. Furthermore, Kank inhibits insulin and active Akt-dependent activation of RhoA through binding to 14-3-3. Based on these findings, we hypothesize that Kank negatively regulates the formation of actin stress fibers and cell migration through the inhibition of RhoA activity, which is controlled by binding of Kank to 14-3-3 in PI3K–Akt signaling.

Abbreviations used in this paper: esiRNA, endoribonuclease-prepared siRNA; GSK3β, glycogen synthase kinase 3β; HEK, human embryonic kidney; IGF-1, insulin-like growth factor 1; IMCD, inner medullary collecting duct; IRS, insulin receptor substrate; MBP, maltose-binding protein; PI3K, phosphoinositide-3 kinase; PIP3, phosphatidylinositol 3,4,5-triphosphate; RBD, RhoA-binding domain; RCC, renal cell carcinoma; ROCK; Rho-associated kinase.

© 2008 Kakinuma et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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