Association of the tyrosine phosphatase SHP-2 with transducin-alpha and a 97-kDa tyrosine-phosphorylated protein in photoreceptor rod outer segments

Increasing evidence indicates that tyrosine phosphorylation, controlled by the concerted action of tyrosine kinases and protein tyrosine phosphatases (PTPs), plays important roles in retinal photoreceptor rod outer segments ( ROS). We characterized PTP activity in isolated bovine ROS that is signific antly inhibited by orthovanadate. Incubating ROS in the presence of exogeno us Mg2+, ATP, and orthovanadate dramatically enhanced the tyrosine phosphor ylation of several endogenous proteins. SHP-2, a PTP with two SH2 domains, was identified in ROS by immunoblot analysis and was found to associate wit h ROS membranes. Immunocytochemistry showed localization of SHP-2 in photor eceptor outer segments and possibly in the outer plexiform, inner nuclear, and inner plexiform cell layers of the retina as well. SHP-2 associated wit h transducin-alpha and a 97-kDa tyrosine-phosphorylated protein in ROS, sug gesting the formation of a multimeric signaling complex. Based on its assoc iation with transducin-alpha and a 97-kDa protein, SHP-2 may regulate the t yrosine phosphorylation of endogenous proteins, including transducin-alpha, and may play a significant role in a novel signaling pathway in photorecep tors.