Amyloid precursor-like protein 2 association with HLA class I molecules.
Amyloid precursor-like protein 2 (APLP2) is a ubiquitously expressed protein. The previously demonstrated functions for APLP2 include binding to the mouse major histocompatibility complex (MHC) class I molecule H-2K(d) and down regulating its cell surface expression. In this study, we have investigated the interaction of APLP2 with the human leukocyte antigen (HLA) class I molecule in human tumor cell lines. APLP2 was readily detected in pancreatic, breast, and prostate tumor lines, although it was found only in very low amounts in lymphoma cell lines. In a pancreatic tumor cell line, HLA class I was extensively co-localized with APLP2 in vesicular compartments following endocytosis of HLA class I molecules. In pancreatic, breast, and prostate tumor lines, APLP2 was bound to the HLA class I molecule. APLP2 was found to bind to HLA-A24, and more strongly to HLA-A2. Increased expression of APLP2 resulted in reduced surface expression of HLA-A2 and HLA-A24. Overall, these studies demonstrate that APLP2 binds to the HLA class I molecule, co-localizes with it in intracellular vesicles, and reduces the level of HLA class I molecule cell surface expression.
Tuli
Amit
A
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
Sharma
Mahak
M
Wang
Xiaojian
X
Simone
Laura C
LC
Capek
Haley L
HL
Cate
Steven
S
Hildebrand
William H
WH
Naslavsky
Naava
N
Caplan
Steve
S
Solheim
Joyce C
JC
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015234:HLA-A Antigens / Q000378:metabolism*; D015789:HLA-A2 Antigen / Q000378:metabolism*; D059871:HLA-A24 Antigen; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured
C084104:APLP2 protein, human; D016564:Amyloid beta-Protein Precursor; D015234:HLA-A Antigens; D015789:HLA-A2 Antigen; D059871:HLA-A24 Antigen; D015395:Histocompatibility Antigens Class I; D009419:Nerve Tissue Proteins