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We have recently shown that a critical regulatory node in the platelet signaling network lies immediately downstream of platelet receptors for thrombin and TxA2. This node is comprised of a scaffold protein (spinophilin, SPL), a protein tyrosine phosphatase (SHP-1), and either of the two members of the Regulators of G protein Signaling family predominantly expressed in platelets (RGS10 or RGS18). The SPL/RGS/SHP-1 complex is present in resting platelets, dissociating when thrombin or TxA2, but not ADP or collagen, activate SHP-1 and release RGS10 and RGS18 to dampen signaling. Here we demonstrate an additional regulatory role for spinophilin, showing that dissociation of SHP-1 from spinophilin is followed by an increase in the binding of spinophilin to PP1, a serine/threonine phosphatase whose binding site maps to a region close to the SHP-1 binding site. The increase in PP1 binding to spinophilin is limited to platelet agonists that cause dissociation of the complex and is selective for the α and γ isoforms of PP1. Studies in cell culture show that SHP-1 and PP1 can compete for binding to spinophilin and that binding inhibits PP1 activity since over-expression of wild type spinophilin, but not spinophilin with a disabled PP1 binding site, causes an increase in the phosphorylation of myosin light chain, a well-characterized PP1 substrate. Collectively, these results indicate that in addition to regulating RGS protein availability in resting platelets, spinophilin can serve as a time-dependent, agonist- and isoform-selective regulator of PP1, inhibiting its activity when decay of the SPL/RGS/SHP-1 complex releases SHP-1 from spinophilin, exposing a binding site for PP1.

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BACKGROUND: Single-center data suggest that general surgery residents perform more cases related to their future fellowship compared with their peers. This study aimed to determine whether this experience was true for residents across multiple programs. STUDY DESIGN: Data from graduates of 18 Accreditation Council for Graduate Medical Education (ACGME)–accredited general surgery residency programs in the US Resident OPerative Experience (ROPE) Consortium were analyzed. Residents were categorized as entering 1 of 12 fellowships or entering directly into general surgery practice. Case log operative domains were mapped to each fellowship, and analyses were performed between groups. RESULTS: Of 1,192 graduated general surgery residents, 955 (80%) pursued fellowship training whereas 235 (20%) went directly into general surgery practice. The top 3 fellowships pursued were trauma/surgical critical care (18%), vascular surgery (13%), and minimally invasive surgery (12%). Residents entering minimally invasive surgery performed the most total cases, whereas residents pursuing breast performed the least (1,209 [1,056–1,325] vs 1,091 [1,006–1,171], p < 0.01). For each fellowship type, graduates completed more total fellowship-specific cases in their future specialty compared with their peers (all p < 0.05). This association was observed for all 12 fellowships at the surgeon chief level (all p < 0.05) and for 10 of 12 fellowships at the surgeon junior level (all p < 0.05). CONCLUSIONS: General surgery residents perform more cases related to their future specialty choice compared with their peers. These data suggest that the specialization process begins during residency. This tendency among residents should be considered as general surgery residency undergoes structural redesign in the future.

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