The protein kinase domains of v‐kit, the oncogene of the acute transforming feline retrovirus HZ4‐FeSV (HZ4‐feline sarcoma virus), CSF‐1R (macrophage colony stimulating factor receptor) and PDGFR (platelet derived growth factor receptor) display extensive homology. Because of the close structural relationship of v‐kit, CSF‐1R and PDGFR we predicted that c‐kit would encode a protein kinase transmembrane receptor (Besmer et al., 1986a; Yarden et al., 1986). We have now determined the primary structure of murine c‐kit from a DNA clone isolated from a brain cDNA library. The nucleotide sequence of the c‐kit cDNA predicts a 975 amino acid protein product with a calculated mol. wt of 109.001 kd. It contains an N‐terminal signal peptide, a transmembrane domain (residues 519‐543) and in the C‐terminal half the v‐kit homologous sequences (residues 558‐925). c‐kit therefore contains the features which are characteristic of a transmembrane receptor kinase. Comparison of c‐kit, CSF‐1R and PDGFR revealed a unique structural relationship of these receptor kinases suggesting a common evolutionary origin. The outer cellular domain of c‐kit was shown to be related to the immunoglobulin superfamily. The sites of expression of c‐kit in normal tissue predict a function in the brain and in hematopoietic cells. N‐terminal sequences which include the extracellular domain and the transmembrane domain as well as 50 amino acids from the C‐terminus of c‐kit are deleted in v‐kit. These structural alterations are likely determinants of the oncogenic activation of v‐kit.(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of concentrated cell-free extracellular material from stationary-phase cultures of Burkholderia cepacia 10661 and Pseudomonas aeruginosa PAO1 on virulence factor production in B. cepacia was assessed. While increasing concentrations of the B. cepacia exoproduct caused a slight increase in siderophore, lipase, and protease production in the producing organism, a significant increase in productivity was observed for all three virulence factors with the addition of the PAO1 exoproduct. Moreover, the addition of the exoproduct from a strain of P. aeruginosa producing reduced amounts of autoinducer caused only a slightly greater response than that of the control. Both B. cepacia 10661 and P. aeruginosa PAO1, along with two matched clinical isolates of both organisms obtained from a cystic fibrotic patient, were shown to produce variable amounts of three different types of autoinducer. The potential for interspecies signalling in microbial pathogenicity is discussed.Burkholderia cepacia, formerly known as Pseudomonas cepacia, is now recognized as an important opportunistic agent of human disease (6,8). In particular, it has received a great deal of attention owing to its increasing association with fatal pulmonary infections in patients with cystic fibrotic (CF) lung disease (9, 13). Clinically, B. cepacia colonization of CF patients can result in an asymptomatic carriage, a slow and continuous decline in lung function, or third, a rapid deterioration of the lung accompanied by fever, necrotizing pneumonia, and in some cases, bacteremia (6, 9). This third syndrome is not observed with other CF pathogens. Generally, it has been noted that B. cepacia colonizes the lung after infection by other microorganisms (24,25). Indeed, in a recent survey of the population with CF lung disease in Greater Manchester, England, only 3.3% of patients were colonized exclusively with B. cepacia (11). Instead, over 80% of the patients were cocolonized with P. aeruginosa. Whereas P. aeruginosa produces a panoply of virulence factors which play an active role in the organism's pathogenicity (7,26), little is known about the pathophysiology of B. cepacia (5,14). Isolated strains of B. cepacia are variable in their abilities to produce hemolysins, lipase and protease (5), exopolysaccharide (2, 17), and ironchelating siderophores (12, 21) in vitro. Consequently, there has been no direct correlation with any of these virulence factors to the organism's pathogenic status in vivo. However, a novel possibility might be the active coaggregation of B. cepacia and P. aeruginosa in the lungs, whereby one species synergistically enhances the virulence determinants of the other. To this effect, the enhancement of B. cepacia attachment to different surfaces by P. aeruginosa exoproducts has been demonstrated (1, 18).It is now recognized that individual cells within a multicellular system can both generate signals and respond to those produced by the surrounding cells, providing a basis for cells to change in response to prevailing environmental...
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