Characterization of the divergent eosinophil ribonuclease, mEar 6, and its expression in response to Schistosoma mansoni infection in vivo.
The eosinophil-associated ribonucleases (Ears) are rapidly evolving proteins found in multigene clusters that are unique to each rodent species. Of the 15 independent genes in the Mus musculus cluster, only mEars 1 and 2 are expressed at significant levels at homeostasis. Here we characterize the expression of mEar 6 in the liver and spleen in mice in response to infection with the helminthic parasite, Schistosoma mansoni. Interestingly, expression of mEar 6 is not directly related to the elevated levels of serum IL-5 or tissue eosinophilia characteristic of this disease, as no mEar 6 transcripts were detected in the liver or the spleen from uninfected IL-5-transgenic mice. The coding sequence of mEar 6 has diverged under positive selection pressure (K(a)/K(s) > 1.0) and has a unique unpaired cysteine near the carboxy-terminus of the protein. The high catalytic efficiency of recombinant mEar 6 (k(cat)/K(m) = 0.9 x 10(6)/M/s) is similar to that of the cluster's closest human ortholog, eosinophil-derived neurotoxin (EDN/RNase 2). In summary, we have identified mEar 6 as one of only two RNase A superfamily ribonucleases known to be expressed specifically in response to pathophysiologic stress in vivo.
Nitto
T
T
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, room 11N104, 9000 Rockville Pike, Bethesda, MD 20892, USA. tnitto@niaid.nih.gov
Dyer
K D
KD
Mejia
R A
RA
Byström
J
J
Wynn
T A
TA
Rosenberg
H F
HF
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D017931:DNA Primers; D047150:Eosinophil Cationic Protein / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D015870:Gene Expression; D015151:Immunoblotting; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000378:metabolism; D012550:Schistosoma mansoni; D012555:Schistosomiasis mansoni / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012641:Selection, Genetic; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013154:Spleen / Q000378:metabolism / Q000473:pathology
D017931:DNA Primers; D011994:Recombinant Proteins; D047150:Eosinophil Cationic Protein