RT Journal Article SR Electronic T1 Activated by Stretch JF Science's STKE JO Sci. STKE FD American Association for the Advancement of Science SP tw8 OP tw8 DO 10.1126/stke.2001.74.tw8 VO 2001 IS 74 YR 2001 UL http://stke.sciencemag.org/content/2001/74/tw8.abstract AB Using a special culture system that can be biaxially expanded, Sawada et al. exposed cultured fibroblasts to stretch forces and contraction forces. The activities of the mitogen-activated protein kinases, ERK, JNK, and p38, increased when the cells were stretched. ERK, p38, and to a lesser degree, JNK activities were all inhibited by forced cell contraction. The activities of the small guanosine triphosphatases (GTPases), Ras and Rap1, were inversely regulated, with Ras inhibited by stretch and activated by contraction, and Rap1 activated by stretch and inhibited by contraction. Inhibition of Rap1 by expression of a Rap1 GTPase-activating protein inhibited the activation of p38 specifically, and overexpression of Rap1 stimulated p38 activity, placing Rap1 as a key upstream regulator of p38 activity during stretch responses. Y. Sawada, K. Nakamura, K. Doi, K. Takeda, K. Tobiume, M. Saitoh, K. Morita, I. Komuro, K. De Vos, M. Sheetz, H. Ichijo, Rap1 is involved in cell stretching modulation of p38 but not ERK and JNK MAP kinase. J. Cell Sci. 114, 1221-1227 (2001). [Online Journal]