title: Proteome analysis of distinct developmental stages of human natural killer (NK) cells.
abstract: The recent Natural Killer (NK) cell maturation model postulates that CD34(+) hematopoietic stem cells (HSC) first develop into CD56(bright) NK cells, then into CD56(dim)CD57(-) and finally into terminally maturated CD56(dim)CD57(+). The molecular mechanisms of human NK cell differentiation and maturation however are incompletely characterized. Here we present a proteome analysis of distinct developmental stages of human primary NK cells, isolated from healthy human blood donors. Peptide sequencing was used to comparatively analyze CD56(bright) NK cells versus CD56(dim) NK cells and CD56(dim)CD57(-) NK cells versus CD56(dim)CD57(+) NK cells and revealed distinct protein signatures for all of these subsets. Quantitative data for about 3400 proteins were obtained and support the current differentiation model. Furthermore, 11 donor-independently, but developmental stage specifically regulated proteins so far undescribed in NK cells were revealed, which may contribute to NK cell development and may elucidate a molecular source for NK cell effector functions. Among those proteins, S100A4 (Calvasculin) and S100A6 (Calcyclin) were selected to study their dynamic subcellular localization. Upon activation of human primary NK cells, both proteins are recruited into the immune synapse (NKIS), where they colocalize with myosin IIa.
authors: Research Group Cellular Proteomics, Helmholtz Centre for Infection Research, HZI, Inhoffenstraβe 7, D-38124 Braunschweig, Germany.
authors: Maxi
authors: M
authors: Scheiter
authors: Ulrike
authors: U
authors: Lau
authors: Marco
authors: M
authors: van Ham
authors: Björn
authors: B
authors: Bulitta
authors: Lothar
authors: L
authors: Gröbe
authors: Henk
authors: H
authors: Garritsen
authors: Frank
authors: F
authors: Klawonn
authors: Sebastian
authors: S
authors: König
authors: Lothar
authors: L
authors: Jänsch
mesh_terms: D000595:Amino Acid Sequence; D019002:CD56 Antigen / Q000378:metabolism; D018959:CD57 Antigens / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism; D002454:Cell Differentiation; D002469:Cell Separation; D002478:Cells, Cultured; D006801:Humans; D054992:Immunological Synapses / Q000378:metabolism; D007694:Killer Cells, Natural / Q000502:physiology*; D008213:Lymphocyte Activation; D058977:Molecular Sequence Annotation; D008969:Molecular Sequence Data; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism; D021381:Protein Transport; D020543:Proteome / Q000737:chemistry / Q000378:metabolism*; D000075383:S100 Calcium Binding Protein A6; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D019002:CD56 Antigen; D018959:CD57 Antigens; D018797:Cell Cycle Proteins; C522918:NCAM1 protein, human; D020543:Proteome; D000075383:S100 Calcium Binding Protein A6; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C055351:S100A6 protein, human; C077591:S100A4 protein, human; D024507:Nonmuscle Myosin Type IIA