1. Signaling pathways influencing SLF and c-kit-mediated survival and proliferation
Stuart A Berger Immunol Res . 2006;35(1-2):1-12. doi: 10.1385/IR:35:1:1.
Steel factor (SLF) and c-Kit are a ligand-receptor pair that regulates growth and activation of a variety of hemopoietic and non-hemopoietic cells. This review describes our work investigating downstream signaling pathways activated by SLF, with particular emphasis on signaling differences associated with soluble vs membrane- bound ligand, and our identification of an important role for PLC activation and Ca2+ influx in supporting c-Kit positive cells in vitro and in vivo. This work led to the identification of a unique form of cell death termed activation enhanced cell death (AECD) that involves stimulating a cell with a growth or activation signal while concurrently blocking Ca2+ influx. Approaches that we have taken toward identifying cellular factors associated with sensitivity and resistance to AECD are summarized, as is our experience with a variety of experimental models. The use of econazole as a calcium channel blocker and its mechanism of action are described, as is its potential for development as an anticancer therapeutic.
2. The Steel factor
A E Namen, M B Widmer, S D Lyman, P de Vries, D E Williams Dev Biol . 1992 Jun;151(2):368-76. doi: 10.1016/0012-1606(92)90176-h.
Steel factor (SLF) is a recently identified growth factor which is the gene product of the murine Steel locus and a ligand for the c-kit tyrosine kinase receptor, the product of the dominant white spotting locus (W). Defects at these genetic loci result in aberrant melanocyte, germ cell, and hematopoietic development. Both the receptor (c-kit) and the ligand (SLF) have been shown to undergo tissue-specific mRNA splicing to produce distinct isoforms which have unique biological functions. As predicted by the phenotype of these mutations, SLF influences the growth and differentiation of melanocytes, primordial germ cells, and a broad spectrum of cell types in the hematopoietic progenitor and stem cell hierarchy. SLF has also been shown to have effects on hematopoietic lineages not predicted by defects seen in the Steel mouse.
3. SCF(SLF)-mediated cytosolic degradation of S-RNase is required for cross-pollen compatibility in S-RNase-based self-incompatibility in Petunia hybrida
Yu'e Zhang, Jiangbo Fan, Yongbiao Xue, Wei Liu, Qun Li, Junhui Li, Yanzhai Song Front Genet . 2014 Jul 22;5:228. doi: 10.3389/fgene.2014.00228.
Many flowering plants adopt self-incompatibility (SI) to maintain their genetic diversity. In species of Solanaceae, Plantaginaceae, and Rosaceae, SI is genetically controlled by a single S-locus with multiple haplotypes. The S-locus has been shown to encode S-RNases expressed in pistil and multiple SLF (S-locus F-box) proteins in pollen controlling the female and male specificity of SI, respectively. S-RNases appear to function as a cytotoxin to reject self-pollen. In addition, SLFs have been shown to form SCF (SKP1/Cullin1/F-box) complexes to serve as putative E3 ubiquitin ligase to interact with S-RNases. Previously, two different mechanisms, the S-RNase degradation and the S-RNase compartmentalization, have been proposed as the restriction mechanisms of S-RNase cytotoxicity allowing compatible pollination. In this study, we have provided several lines of evidence in support of the S-RNase degradation mechanism by a combination of cellular, biochemical and molecular biology approaches. First, both immunogold labeling and subcellular fractionation assays showed that two key pollen SI factors, PhS3L-SLF1 and PhSSK1 (SLF-interacting SKP1-like1) from Petunia hybrida, a Solanaceous species, are co-localized in cytosols of both pollen grains and tubes. Second, PhS3L-RNases are mainly detected in the cytosols of both self and non-self-pollen tubes after pollination. Third, we found that PhS-RNases selectively interact with PhSLFs by yeast two-hybrid and co-immunoprecipitation assays. Fourth, S-RNases are specifically degraded in compatible pollen tubes by non-self SLF action. Taken together, our results demonstrate that SCF(SLF-mediated) non-self S-RNase degradation occurs in the cytosol of pollen tube through the ubiquitin/26S proteasome system serving as the major mechanism to neutralize S-RNase cytotoxicity during compatible pollination in P. hybrida.
