TY - JOUR
T1 - Rho-kinase modulates the function of STEF, a Rac GEF, through its phosphorylation
AU - Takefuji, Mikito
AU - Mori, Kazutaka
AU - Morita, Yasuhiro
AU - Arimura, Nariko
AU - Nishimura, Takashi
AU - Nakayama, Masanori
AU - Hoshino, Mikio
AU - Iwamatsu, Akihiro
AU - Murohara, Toyoaki
AU - Kaibuchi, Kozo
AU - Amano, Mutsuki
N1 - Funding Information:
We thank Dr. T. Watanabe and Dr. S. Wang for helpful discussion and preparation of some materials, Mrs. T. Ishii for secretarial assistance. This research was supported in part by Grants-in-Aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) and the Japan Society for the Promotion of Science (JSPS); a Grant-in-Aid for Creative Scientific Research from JSPS; The 21st Century Centre of Excellence Program from MEXT; and the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation.
PY - 2007/4/13
Y1 - 2007/4/13
N2 - Rho family GTPases are key regulators of various physiological processes. Several recent studies indicated that the antagonistic relationship between Rho and Rac is essential for cell polarity and that the Rac activity is negatively regulated by Rho. In this study, we found that Rho-kinase, an effector of Rho, counteracted the Rac GEF STEF-induced Rac1 activation in COS7 cells. Rho-kinase phosphorylated STEF at Thr1662 in vitro, and Y-27632, a Rho-kinase inhibitor, suppressed lysophosphatidic acid-induced phosphorylation of STEF in PC12D cells. STEF interacted with specific molecules such as microtubule-associated protein 1B, and the phosphorylation of STEF by Rho-kinase diminished its interaction with these molecules. STEF promoted nerve growth factor-induced neurite outgrowth in PC12D cells, while the phosphomimic mutant of STEF had a weakened ability to enhance neurite outgrowth. Taken together, these results suggest that the phosphorylation of STEF by Rho-kinase exerts the inhibitory effect on the function of STEF.
AB - Rho family GTPases are key regulators of various physiological processes. Several recent studies indicated that the antagonistic relationship between Rho and Rac is essential for cell polarity and that the Rac activity is negatively regulated by Rho. In this study, we found that Rho-kinase, an effector of Rho, counteracted the Rac GEF STEF-induced Rac1 activation in COS7 cells. Rho-kinase phosphorylated STEF at Thr1662 in vitro, and Y-27632, a Rho-kinase inhibitor, suppressed lysophosphatidic acid-induced phosphorylation of STEF in PC12D cells. STEF interacted with specific molecules such as microtubule-associated protein 1B, and the phosphorylation of STEF by Rho-kinase diminished its interaction with these molecules. STEF promoted nerve growth factor-induced neurite outgrowth in PC12D cells, while the phosphomimic mutant of STEF had a weakened ability to enhance neurite outgrowth. Taken together, these results suggest that the phosphorylation of STEF by Rho-kinase exerts the inhibitory effect on the function of STEF.
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U2 - 10.1016/j.bbrc.2007.02.028
DO - 10.1016/j.bbrc.2007.02.028
M3 - Article
C2 - 17320046
AN - SCOPUS:33847305415
SN - 0006-291X
VL - 355
SP - 788
EP - 794
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -