A role for the MHC class I-like Mill molecules in nutrient metabolism and wound healing.
MHC class I family members serve multiple functions beyond antigen presentation. We provide insight into the structure, expression and function of the Mill subfamily. This family includes two surface glycoproteins, Mill1 and Mill2. Protein sequences for Mill1 and Mill2 are most highly related to the NKG2D ligands, MICA and MICB, but neither of them bound to NKG2D. Computer-based protein modelling indicated that hereditary haemochromatosis protein (HFE), a molecule involved in iron uptake, was most similar. Mill1 and Mill2 were observed on cycling thymocytes, proliferating smooth muscle cells and fibroblasts. Using soluble Mill proteins, we found evidence for a soluble ligand in serum. Like HFE, the Mill family may be involved in nutrient metabolism. Skin was one of the only three organs found to express transcripts for both Mill1 and Mill2. Addition of antibodies specific for Mill2 to wounded skin enhanced healing. Our results suggest a role for the Mill proteins in cellular metabolism, with possible therapeutic significance.
The Department of Oncology, Amgen Washington, Seattle, WA, USA. brabinov@mdanderson.org
Brian A
BA
Rabinovich
Randal R
RR
Ketchem
Martin
M
Wolfson
Lynn
L
Goldstein
Marylin
M
Skelly
David
D
Cosman
D017398:Alternative Splicing; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D003001:Cloning, Molecular; D003198:Computer Simulation; D005260:Female; D005347:Fibroblasts; D005434:Flow Cytometry; D005805:Genes, MHC Class I / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000737:chemistry; D008562:Membrane Glycoproteins / Q000502:physiology*; D008565:Membrane Proteins / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009924:Organ Culture Techniques; D051381:Rats; D011917:Rats, Inbred Lew; D012867:Skin / Q000378:metabolism; D013601:T-Lymphocytes; D013950:Thymus Gland / Q000378:metabolism; D014599:Uterus / Q000502:physiology; D014945:Wound Healing / Q000502:physiology*; D001613:beta 2-Microglobulin / Q000378:metabolism
D000071020:Hemochromatosis Protein; C499535:Hfe protein, mouse; D015395:Histocompatibility Antigens Class I; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C532300:Mill1 protein, mouse; C532301:Mill2 protein, mouse; D001613:beta 2-Microglobulin; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins