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Characterization of the tammar wallaby ( Macropus eugenii ) whey acidic protein gene; new insights into the function of the protein
Author(s) -
Topcic Denijal,
Auguste Aurelie,
De Leo Alison A.,
Lefevre Christophe,
Digby Matthew R.,
Nicholas Kevin R.
Publication year - 2009
Publication title -
evolution and development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.651
H-Index - 78
eISSN - 1525-142X
pISSN - 1520-541X
DOI - 10.1111/j.1525-142x.2009.00343.x
Subject(s) - tammar wallaby , biology , cyclin d1 , gene , microbiology and biotechnology , function (biology) , cell growth , genetics , cell cycle
SUMMARY Whey acidic protein (WAP) belongs to a family of four disulfide core (4‐DSC) proteins rich in cysteine residues and is the principal whey protein found in milk of a number of mammalian species. Eutherian WAPs have two 4‐DSC domains, whereas marsupial WAPs are characterized by the presence of an additional domain at the amino terminus. Structural and expression differences between marsupial and eutherian WAPs have presented challenges to identifying physiological functions of the WAP protein. We have characterized the genomic structure of tammar WAP (tWAP) gene, identified its chromosomal localization and investigated the potential function of tWAP. We have demonstrated that tWAP and domain III (DIII) of the protein alone stimulate proliferation of a mouse mammary epithelial cell line (HC11) and primary cultures of tammar mammary epithelial cells (Wall‐MEC), whereas deletion of DIII from tWAP abolishes this proliferative effect. However, tWAP does not induce proliferation of human embryonic kidney (HEK293) cells. DNA synthesis and expression of cyclin D1 and cyclin‐dependent kinase‐4 genes were significantly up‐regulated when Wall‐MEC and HC11 cells were grown in the presence of either tWAP or DIII. These data suggest that DIII is the functional domain of the tWAP protein and that evolutionary pressure has led to the loss of this domain in eutherians, most likely as a consequence of adopting a reproductive strategy that relies on greater investment in development of the newborn during pregnancy.