TY - JOUR
T1 - Clara cell 10 kDa protein (CC10)
T2 - Comparison of structure and function to uterogloblin
AU - Singh, Gurmukh
AU - Katyal, Sikandar L.
AU - Brown, William E.
AU - Kennedy, Amy L.
AU - Singh, Ushasi
AU - Wong-Chong, Mari Lou
N1 - Funding Information:
This work was supported by the Department of Veterans Affairs and PHS Grants HL 37739 and HL 28193 and the Pathology Education and Research Foundation of the University of Pittsburgh School of Medicine. The authors wish to thank Dr. Mornon for providing the coordinates of X-ray diffraction data for rabbit uteroglobin.
PY - 1990/7/6
Y1 - 1990/7/6
N2 - The cellular localization, functional activities and structure of rat and human Clara cell 10 kDa proteins (CC10) are compared to rabbit uteroglobin. CC10 is present exclusively in the non-ciliated cells of the surface epithelium of the pulmonary airways, whereas uteroglobin is reported to be present in the lung and reproducted organs. There is about 55% identity between the amino acid sequences of rat CC10 and either rabbit uteroglobin or human CC10. The latter two have 61% identity. Using the known structure of uteroglobin as the model, correclations between the structure and function for this group of proteins are made. Substitution of the residues for the rat and human CC10 into the structure of uteroglobin suggests that these proteins may be members of a structurally homologous family. Some of the functional differences may be due to distortion of the hydrophobic pocket in the dimeric protein and a surface hypervariability located on one contiguous helix and β turn. Rat CC10 and rabbit uteroglobin both, nearly equally, inhibit papain and bind progesterone. Human CC10 does not inhibit papain and has markedly lower progesterone binding (4.6% of rabbit uteroglobin). Antiinflammatory activity of synthetic peptides corresponding to a homologous sequence region of uteroglobin and the two Clara cell proteins was tested. The region chosen has sequence similarity to lipoeortin I. The peptides not only failed to inhibit carrageenan-induced foot pad swelling but exacerbated it. All three proteins inhibit pancreatic phospholipase A2. The phospholipase A2 inhibitory effect of the CC10 may be important in regulating the inflammatory responses in the lung.
AB - The cellular localization, functional activities and structure of rat and human Clara cell 10 kDa proteins (CC10) are compared to rabbit uteroglobin. CC10 is present exclusively in the non-ciliated cells of the surface epithelium of the pulmonary airways, whereas uteroglobin is reported to be present in the lung and reproducted organs. There is about 55% identity between the amino acid sequences of rat CC10 and either rabbit uteroglobin or human CC10. The latter two have 61% identity. Using the known structure of uteroglobin as the model, correclations between the structure and function for this group of proteins are made. Substitution of the residues for the rat and human CC10 into the structure of uteroglobin suggests that these proteins may be members of a structurally homologous family. Some of the functional differences may be due to distortion of the hydrophobic pocket in the dimeric protein and a surface hypervariability located on one contiguous helix and β turn. Rat CC10 and rabbit uteroglobin both, nearly equally, inhibit papain and bind progesterone. Human CC10 does not inhibit papain and has markedly lower progesterone binding (4.6% of rabbit uteroglobin). Antiinflammatory activity of synthetic peptides corresponding to a homologous sequence region of uteroglobin and the two Clara cell proteins was tested. The region chosen has sequence similarity to lipoeortin I. The peptides not only failed to inhibit carrageenan-induced foot pad swelling but exacerbated it. All three proteins inhibit pancreatic phospholipase A2. The phospholipase A2 inhibitory effect of the CC10 may be important in regulating the inflammatory responses in the lung.
KW - Clara cell 10 kDa protein
KW - Immunohistochemistry
KW - Phospholipase A inhibitor
KW - Progestone Antiinflammatory activity
KW - Proteinase inhibitor
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U2 - 10.1016/0167-4838(90)90270-P
DO - 10.1016/0167-4838(90)90270-P
M3 - Article
C2 - 2378892
AN - SCOPUS:0025310130
SN - 0167-4838
VL - 1039
SP - 348
EP - 355
JO - Biochimica et Biophysica Acta (BBA)/Protein Structure and Molecular
JF - Biochimica et Biophysica Acta (BBA)/Protein Structure and Molecular
IS - 3
ER -