The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.
The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.
Patent No.:
Date of Patent:
Jan. 01, 2002
Filed:
Jun. 30, 1997
Shu Chien, La Jolla, CA (US);
John Y-J Shyy, San Diego, CA (US);
University of California at San Diego, La Jolla, CA (US);
Abstract
Hemodynamic forces play a key role in inducing 2, theroscler-osis-implicated gene in Vascular endothelial cells. To ellcitate the signal transduction pathway leading to such gene expression, the effects of fluid shearing on the activities of upstream signaling molecules is reported here. Fluid shearing (shear stress=12 dynes/cm ) induced a transient and rapid activation of p21 and preferentially activated c-jun NH terminal kinases (JNK 1, 2) over extracellular signal-regulated kinases (ERK-1, -2). Co-transfection of RasNI7, a dominant negative mutant of Ha-Ras, attenuated the shear-activated JNK and luciferase reporters driven by TPA-responsive elements. JNIK(K-R) and MEKK(K-M), the respective catalytically inactive mutants of JNKI and MEKK, also partially inhibited the shear-induced luciferase reporters. In contrast, Raf301, ERK(K71R), and ERK(K52R), the dominant negative mutants of Raf-1, ERK-1, and ERK-2, respectively, had little effects on the activities of these reporters. The activation of JNK was also correlated with an increased c-Jun transcriptional activity, which was attenuated by a negative mutant of Son of sevenless (Sos). Thus, mechanical stimulation exerted by fluid shearing activates, primarily the Ras-MEKK-JNK pathway in inducing endothelial gene expression.