S. 2019. "A comprehensive genome variation map of melon identifies multiple domestication events and loci influencing agronomic traits". Nature Genetics.

Chemotaxis plays an important role in cancer cell metastasis. In this study, we showed that epidermal growth factor (EGF) was a more potent chemoattractant than chemokine SDF-1a/ CXCL12 for human breast cancer cell MDA-MB-231. Different inhibitors were used to evaluate the involvement of 12 protein kinase C (PKC) isotypes in the chemotactic signaling pathway. Chelerythrine chloride, an inhibitor of all PKC isotypes, blocked chemotaxis, whereas inhibitors of classic and novel PKC, such as Gö6976, Gö6850, or calphostin C, only impaired EGF-induced chemotaxis to a minor extent by e32% inhibition. These data suggested that atypical PKC were involved. The ligand-induced actin polymerization and cell adhesion were also similarly dependent on atypical PKC. Immunofluorescent staining showed an EGF-induced, LY294002-sensitive translocation of PKCf from the cytosol to the plasma membrane, indicating that EGF was capable of activating PKCf, probably via phosphoinositide 3 kinases. A myristoylated PKCf pseudosubstrate blocked the chemotaxis with an IC 50 of 20 Amol/L. To expand our investigation, we further showed that in MCF-7 and T47D, two additional human breast cancer cell lines, EGF-activated PKCf and the PKCf pseudosubstrate, inhibited chemotaxis. Taken together, our data suggest that PKCf is an essential component of the EGFstimulated chemotactic signaling pathway in human breast cancer cells. (Cancer Res 2005; 65(4): 1433-41)

Amyloid-␤, the pathologic protein in Alzheimer's disease, induces chemotaxis and production of reactive oxygen species in phagocytic cells, but mechanisms have not been fully defined. Here we provide three lines of evidence that the phagocyte G protein-coupled receptor (N-formylpeptide receptor 2 (FPR2)) mediates these amyloid-␤-dependent functions in phagocytic cells. First, transfection of FPR2, but not related receptors, including the other known N-formylpeptide receptor FPR, reconstituted amyloid-␤-dependent chemotaxis and calcium flux in HEK 293 cells. Second, amyloid-␤ induced both calcium flux and chemotaxis in mouse neutrophils (which express endogenous FPR2) with similar potency as in FPR2-transfected HEK 293 cells. This activity could be specifically desensitized in both cell types by preincubation with a specific FPR2 agonist, which desensitizes the receptor, or with pertussis toxin, which uncouples it from G i -dependent signaling. Third, specific and reciprocal desensitization of superoxide production was observed when N-formylpeptides and amyloid-␤ were used to sequentially stimulate neutrophils from FPR ؊/؊ mice, which express FPR2 normally. Potential biological relevance of these results to the neuroinflammation associated with Alzheimer's disease was suggested by two additional findings: first, FPR2 mRNA could be detected by PCR in mouse brain; second, induction of FPR2 expression correlated with induction of calcium flux and chemotaxis by amyloid-␤ in the mouse microglial cell line N9. Further, in sequential stimulation experiments with N9 cells, N-formylpeptides and amyloid-␤ were able to reciprocally cross-desensitize each other. Amyloid-␤ was also a specific agonist at the human counterpart of FPR2, the FPR-like 1 receptor. These results suggest a unified signaling mechanism for linking amyloid-␤ to phagocyte chemotaxis and oxidant stress in the brain.