The Src homology 2 (SH2) domains of the p85 subunit of phosphatidylinositol 3-kinase have been shown to bind to the tyrosinephosphorylated platelet-derived growth factor receptor (PDGFR). Previously, we have demonstrated that p85 SH2 domains can also bind to the serine/threonine kinase A-Raf via a unique phosphorylation-independent interaction. In this report, we describe a new phosphotyrosine-independent p85 SH2-binding protein, ankyrin 3 (Ank3). In general, ankyrins serve a structural role by binding to both integral membrane proteins at the plasma membrane and spectrin/fodrin proteins of the cytoskeleton. However, smaller isoforms of Ank3 lack the membrane domain and are localized to late endosomes and lysosomes. We found that p85 binds directly to these smaller 120-and 105-kDa Ank3 isoforms. Both the spectrin domain and the regulatory domain of Ank3 are involved in binding to p85. At least two domains of p85 can bind to Ank3, and the interaction involving the p85 C-SH2 domain was found to be phosphotyrosine-independent. Overexpression of the 120-or 105-kDa Ank3 proteins resulted in significantly enhanced PDGFR degradation and a reduced ability to proliferate in response to PDGF. Ank3 overexpression also differentially regulated signaling pathways downstream from the PDGFR. Chloroquine, an inhibitor of lysosomalmediated degradation pathways, blocked the ability of Ank3 to enhance PDGFR degradation. Immunofluorescence experiments demonstrated that both small Ank3 isoforms colocalized with the lysosomal-associated membrane protein and with p85 and the PDGFR. These results suggest that Ank3 plays an important role in lysosomal-mediated receptor down-regulation, likely through a p85-Ank3 interaction.

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Radial nerve injuries are among the most common major traumatic peripheral nerve injuries. Recent literature has updated our knowledge of aspects ranging from radial nerve anatomy to treatment options. Observation and tendon transfers were, and still are, the mainstays of management. However, the improved outcomes of nerve repair even 5 months after injury have changed the treatment algorithm. Nerve repair techniques using conduits, wraps, autograft, and allograft allow tension-free coaptations to improve success. Nerve transfers have evolved to allow a more anatomic recovery of function if used in a timely manner. This review offers an update on radial nerve injuries that reflects recent advances.