Association of the Tyrosine Phosphatase SHP‐2 with Transducin‐α and a 97‐kDa Tyrosine‐Phosphorylated Protein in Photoreceptor Rod Outer Segments

• Published in: Journal of neurochemistry Vol. 73; no. 6; pp. 2331 - 2340
• Main Authors: Bell, Michael W., Alvarez, Kathy, Ghalayini, Abboud J.
• Format: Journal Article
• Language: English
• Published: Oxford UK Blackwell Science Ltd 01-12-1999; Blackwell
• Subjects: Animals; Biological and medical sciences; Cattle; Enzyme Inhibitors - pharmacology; Eye and associated structures. Visual pathways and centers. Vision; Eye Proteins - antagonists & inhibitors; Eye Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Intracellular Signaling Peptides and Proteins; Macromolecular Substances; Membrane Proteins - metabolism; Molecular Weight; Molybdenum - pharmacology; Phosphorylation; Phosphotyrosine - metabolism; Protein Processing, Post-Translational; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Protein Tyrosine Phosphatase, Non-Receptor Type 6; Protein tyrosine phosphatases; Protein Tyrosine Phosphatases - antagonists & inhibitors; Protein Tyrosine Phosphatases - metabolism; Retina; Rod Cell Outer Segment - enzymology; Rod outer segments; Shp-2 protein; SHP‐2; Subcellular Fractions - enzymology; Transducin; Transducin - metabolism; transducin-^a; Vanadate; Vanadates - pharmacology; Vertebrates: nervous system and sense organs; Enzyme; Rod; Photoreceptor; Phosphoric monoester hydrolases; Transducin; Retina; Ox; Esterases; Eye; Visual system; Vertebrata; Mammalia; Outer segment; Hydrolases; Artiodactyla; Ungulata; Protein-tyrosine-phosphatase
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.1999.0732331.x

: 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 significantly inhibited by orthovanadate.
Incubating ROS in the presence of exogenous Mg2+, ATP, and orthovanadate dramatically enhanced the tyrosine phosphorylation of several endogenous proteins. SHP‐2, a PTP with two SH2 domains, was identified in ROS by immunoblot analysis and was found to associate with ROS membranes. Immunocytochemisry showed localization of SHP‐2 in photoreceptor outer segments and possibly in the outer plexiform, inner nuclear, and inner plexiform cell layers of the retina as well. SHP‐2 associated with transducin‐α and a 97‐kDa tyrosine‐phosphorylated protein in ROS, suggesting the formation of a multimeric signaling complex. Based on its association with transducin‐α and a 97‐kDa protein, SHP‐2 may regulate the tyrosine phosphorylation of endogenous proteins, including transducin‐α, and may play a significant role in a novel signaling pathway in photoreceptors.