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Differential interaction of Cbl with Grb2 and CrkL in CD2-mediated NK cell activation. 2000

J Y Huang, and H Umehara, and H Inoue, and F H Tabassam, and T Okazaki, and T Kono, and Y Minami, and Y Tanaka, and N Domae
Department of Internal Medicine, Osaka Dental University, 8-1 Kuzuha Hanazono-cho, Hirakata-shi, 573-1121, Osaka, Japan.

Natural killer (NK) cells participate in both innate and adoptive immunity by their prompt secretion of cytokines and by their ability to lyse virally infected cells or tumor cells. CD2 is surface glycoprotein receptors and crucial for NK cell activation. However, molecular events involved in CD2-mediated NK cell activation have not been fully elucidated. Cbl-Grb2 and Cbl-CrkL interactions have been implicated in T cell and B cell receptor, and cytokine receptor signaling. Here we analyzed tyrosine phosphorylation and interactions of Cbl with adapter proteins, Grb2 and CrkL, in NK3.3 cells. CD2 crosslinking results in the marked tyrosine phosphorylation of Cbl in an antibody concentration- and time-dependent manner. Immunodepletion studies reveal that Grb2-associated tyrosine phosphorylated p120 kDa protein is Cbl. In vitro binding studies using GST-fusion proteins demonstrate that Cbl constitutively associates with the SH3 domains of Grb2, with a preference for the amino-terminal domain. In addition, we demonstrate that CrkL associates with a large portion of tyrosine phosphorylated Cbl after CD2 stimulation of NK3.3 cells. In contrast to constitutive Cbl association with Grb2, tyrosine phosphorylated Cbl interacts with CrkL via its SH2 domain only after CD2 stimulation. Although the precise roles of interactions of Cbl with Grb2 and CrkL in NK cell activation remains to be elucidated, their tyrosine phosphorylation, in addition to the multiple protein interactions described here, strongly suggest that interactions of Cbl with Grb2 and CrkL may play pivotal roles in CD2-mediated NK cell activation.

UI MeSH Term Description Entries
D007694 Killer Cells, Natural Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type. NK Cells,Natural Killer Cells,Cell, NK,Cell, Natural Killer,Cells, NK,Cells, Natural Killer,Killer Cell, Natural,NK Cell,Natural Killer Cell
D008213 Lymphocyte Activation Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION. Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D009687 Nuclear Proteins Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus. Nucleolar Protein,Nucleolar Proteins,Nuclear Protein,Protein, Nuclear,Protein, Nucleolar,Proteins, Nuclear,Proteins, Nucleolar
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D002352 Carrier Proteins Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes. Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014443 Tyrosine A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin. L-Tyrosine,Tyrosine, L-isomer,para-Tyrosine,L Tyrosine,Tyrosine, L isomer,para Tyrosine
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D015682 Retroviridae Proteins, Oncogenic Retroviral proteins that have the ability to transform cells. They can induce sarcomas, leukemias, lymphomas, and mammary carcinomas. Not all retroviral proteins are oncogenic. Oncogenic Retroviridae Proteins,Proteins, Oncogenic Retroviridae

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