JCB logo
Keystone Symposia
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online May 5, 2008
doi:10.1083/jcb.200707022
The Journal of Cell Biology, Vol. 181, No. 3, 537-549
The Rockefeller University Press, 0021-9525 $30.00
© 2008 Kakinuma et al.
This Article
Right arrow Full Text
Right arrow PDF (Full Text)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via CrossRef
Google Scholar
Right arrow Articles by Kakinuma, N.
Right arrow Articles by Kiyama, R.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kakinuma, N.
Right arrow Articles by Kiyama, R.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

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.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents