title: Matriptase Complexes and Prostasin Complexes with HAI-1 and HAI-2 in Human Milk: Significant Proteolysis in Lactation.
abstract: Significant proteolysis may occur during milk synthesis and secretion, as evidenced by the presence of protease-protease inhibitor complex containing the activated form of the type 2 transmembrane serine protease matriptase and the transmembrane Kunitz-type serine protease inhibitor HAI-1. In order to identify other proteolysis events that may occur during lactation, human milk was analyzed for species containing HAI-1 and HAI-2 which is closely related to HAI-1. In addition to the previously demonstrated matriptase-HAI-1 complex, HAI-1 was also detected in complex with prostasin, a glycosylphosphatidylinositol (GPI)-anchored serine protease. HAI-2 was also detected in complexes, the majority of which appear to be part of higher-order complexes, which do not bind to ionic exchange columns or immunoaffinity columns, suggesting that HAI-2 and its target proteases may be incorporated into special protein structures during lactation. The small proportion HAI-2 species that could be purified contain matriptase or prostasin. Human mammary epithelial cells are the likely cellular sources for these HAI-1 and HAI-2 complexes with matriptase and prostasin given that these protease-inhibitor complexes with the exception of prostasin-HAI-2 complex were detected in milk-derived mammary epithelial cells. The presence of these protease-inhibitor complexes in human milk provides in vivo evidence that the proteolytic activity of matriptase and prostasin are significantly elevated at least during lactation, and possibly contribute to the process of lactation, and that they are under tight control by HAI-1 and HAI-2.
authors.affiliation: Department of Dentistry Renai Branch, Taipei City Hospital, Taipei, Taiwan.|Graduate Institute of Medical Sciences National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Lai
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, United States of America.
authors.forename: Ying-Jung J
authors.initials: YJ
authors.lastname: Lai
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, United States of America.
authors.forename: Feng-Pai
authors.initials: FP
authors.lastname: Chou
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, United States of America.|Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Hsiang-Hua D
authors.initials: HH
authors.lastname: Chang
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, United States of America.
authors.forename: Chun-Che
authors.initials: CC
authors.lastname: Tseng
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, United States of America.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Johnson
authors.affiliation: Graduate Institute of Medical Sciences National Defense Medical Center, Taipei, Taiwan.|Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Jehng-Kang
authors.initials: JK
authors.lastname: Wang
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, United States of America.
authors.forename: Chen-Yong
authors.initials: CY
authors.lastname: Lin
mesh_terms: D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D007774:Lactation; D042361:Mammary Glands, Human / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D008895:Milk, Human / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D053491:Proteinase Inhibitory Proteins, Secretory / Q000737:chemistry / Q000378:metabolism*; D059748:Proteolysis; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D000099271:Prostasin
chemical_list: D008562:Membrane Glycoproteins; D053491:Proteinase Inhibitory Proteins, Secretory; D012697:Serine Endopeptidases; D000099271:Prostasin; C109149:SPINT1 protein, human; C109148:SPINT2 protein, human; C485595:matriptase