Csk-binding protein mediates sequential enzymatic down-regulation and degradation of Lyn in erythropoietin-stimulated cells

We have shown previously that the Src family kinase Lyn is involved in differentiation signals emanating from activated erythropoietin (Epo) receptors. The importance of Lyn to red cell maturation has been highlighted by Lyn -/- mice developing anemia. Here we show that Lyn interacts with C-terminal Src kinase-binding protein (Cbp), an adaptor protein that recruits negative regulators C-terminal Src kinase (Csk)/Csk-like protein-tyrosine kinase (Ctk). Lyn phosphorylated Cbp on several tyrosine residues, including Tyr 314, which recruited Csk/Ctk to suppress Lyn kinase activity. Intriguingly, phosphorylated Tyr314 also bound suppressor of cytokine signaling 1 (SOCS1), another well characterized negative regulator of cell signaling, resulting in elevated ubiquitination, and degradation of Lyn. In Epo-responsive primary cells and cell lines, Lyn rapidly phosphorylated Cbp, suppressing Lyn kinase activity via Csk/Ctk within minutes of Epo stimulation; hours later, SOCS1 bound to Cbp and was involved in the ubiquitination and turnover of Lyn protein. Thus, a single phosphotyrosine residue on Cbp coordinates a two-phase process involving distinct negative regulatory pathways to inactivate, then degrade, Lyn

Mixed-severity fire regimes: Lessons and hypotheses from the Klamath-Siskiyou Ecoregion

Although mixed-severity fires are among the most widespread disturbances influencing western North American forests, they remain the least understood. A major question is the degree to which mixed-severity fire regimes are simply an ecological intermediate between low- and high-severity fire regimes, versus a unique disturbance regime with distinct properties. The Klamath-Siskiyou Mountains of southwestern Oregon and northwestern California provide an excellent laboratory for studies of mixed-severity fire effects, as structurally diverse vegetation types in the region foster, and partly arise from, fires of variable severity. In addition, many mixed-severity fires have occurred in the region in the last several decades, including the nationally significant 200,000-ha Biscuit Fire. Since 2002, we have engaged in studies of early ecosystem response to 15 of these fires, ranging from determinants of fire effects to responses of vegetation, wildlife, and biogeochemistry. We present here some of our important early findings regarding mixed-severity fire, thereby updating the state of the science on mixed-severity fire regimes and highlighting questions and hypotheses to be tested in future studies on mixed-severity fire regimes. Our studies in the Klamath-Siskiyou Ecoregion suggest that forests with mixed-severity fire regimes are characterized primarily by their intimately mixed patches of vegetation of varied age, resulting from complex variations in both fire frequency and severity and species responses to this variation. Based on our findings, we hypothesize that the proximity of living and dead forest after mixed-severity fire, and the close mingling of early- and late-seral communities, results in unique vegetation and wildlife responses compared to predominantly low- or high-severity fires. These factors also appear to contribute to high resilience of plant and wildlife species to mixed-severity fire in the Klamath-Siskiyou Ecoregion. More informed management of ecosystems with mixed-severity regimes requires understanding of their wide variability in space and time, and the particular ecological responses that this variability elicit