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 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. Immunocytochemistry 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-alpha and a 97-kDa tyrosine-phosphorylated protein in ROS, suggesting the formation of a multimeric signaling complex. Based on its association with transducin-alpha and a 97-kDa protein, SHP-2 may regulate the tyrosine phosphorylation of endogenous proteins, including transducin-alpha, and may play a significant role in a novel signaling pathway in photoreceptors.
Bell
M W
MW
Department of Biochemistry, Baylor College of Medicine, Houston, Texas, USA.
Alvarez
K
K
Ghalayini
A J
AJ
D000818:Animals; D002417:Cattle; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005136:Eye Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000378:metabolism*; D008970:Molecular Weight; D008982:Molybdenum / Q000494:pharmacology; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012374:Rod Cell Outer Segment / Q000201:enzymology*; D013347:Subcellular Fractions / Q000201:enzymology; D015293:Transducin / Q000378:metabolism*; D014638:Vanadates / Q000494:pharmacology
D004791:Enzyme Inhibitors; D005136:Eye Proteins; D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; C044659:molybdate; D019000:Phosphotyrosine; D014638:Vanadates; D008982:Molybdenum; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D015293:Transducin