RAFTK/PYK2-dependent and -independent apoptosis in multiple myeloma cells. 1999

D Chauhan, and T Hideshima, and P Pandey, and S Treon, and G Teoh, and N Raje, and S Rosen, and N Krett, and H Husson, and S Avraham, and S Kharbanda, and K C Anderson
Department of Adult Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.

Related Adhesion Focal Tyrosine Kinase (RAFTK; also known as Pyk2), is a member of the Focal Adhesion Kinase (FAK) subfamily and is activated by TNF alpha, UV light and increases in intracellular calcium levels. However, the function of RAFTK remains largely unknown. Our previous studies demonstrated that treatment with dexamethasone (Dex), ionizing radiation (IR), and anti-Fas mAb induces apoptosis in multiple myeloma (MM) cells. In the present study, we examined the potential role of RAFTK during induction of apoptosis in human MM cells triggered by these three stimuli. Dex-induced apoptosis, in contrast to apoptosis triggered by anti-Fas mAb or IR, is associated with activation of RAFTK. Transient overexpression of RAFTK wild type (RAFTK WT) induces apoptosis, whereas transient overexpression of Kinase inactive RAFTK (RAFTK K-M) blocks Dex-induced apoptosis. In contrast, transient overexpression of RAFTK K-M has no effect on apoptosis triggered by IR or Fas. In Dex-resistant cells, Dex does not trigger either RAFTK activation or apoptosis. Finally, interleukin-6 (IL-6), a known survival factor for MM cells, inhibits both activation of RAFTK and apoptosis of MM.1S cells triggered by Dex. Our studies therefore demonstrate Dex-induced RAFTK-dependent, and IR or Fas induced RAFTK-independent apoptotic signaling cascades in MM cells.

UI MeSH Term Description Entries
D009101 Multiple Myeloma A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY. Myeloma, Plasma-Cell,Kahler Disease,Myeloma, Multiple,Myeloma-Multiple,Myelomatosis,Plasma Cell Myeloma,Cell Myeloma, Plasma,Cell Myelomas, Plasma,Disease, Kahler,Multiple Myelomas,Myeloma Multiple,Myeloma, Plasma Cell,Myeloma-Multiples,Myelomas, Multiple,Myelomas, Plasma Cell,Myelomas, Plasma-Cell,Myelomatoses,Plasma Cell Myelomas,Plasma-Cell Myeloma,Plasma-Cell Myelomas
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
D011505 Protein-Tyrosine Kinases Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors. Tyrosine Protein Kinase,Tyrosine-Specific Protein Kinase,Protein-Tyrosine Kinase,Tyrosine Kinase,Tyrosine Protein Kinases,Tyrosine-Specific Protein Kinases,Tyrosylprotein Kinase,Kinase, Protein-Tyrosine,Kinase, Tyrosine,Kinase, Tyrosine Protein,Kinase, Tyrosine-Specific Protein,Kinase, Tyrosylprotein,Kinases, Protein-Tyrosine,Kinases, Tyrosine Protein,Kinases, Tyrosine-Specific Protein,Protein Kinase, Tyrosine-Specific,Protein Kinases, Tyrosine,Protein Kinases, Tyrosine-Specific,Protein Tyrosine Kinase,Protein Tyrosine Kinases,Tyrosine Specific Protein Kinase,Tyrosine Specific Protein Kinases
D011839 Radiation, Ionizing ELECTROMAGNETIC RADIATION or particle radiation (high energy ELEMENTARY PARTICLES) capable of directly or indirectly producing IONS in its passage through matter. The wavelengths of ionizing electromagnetic radiation are equal to or smaller than those of short (far) ultraviolet radiation and include gamma and X-rays. Ionizing Radiation,Ionizing Radiations,Radiations, Ionizing
D003907 Dexamethasone An anti-inflammatory 9-fluoro-glucocorticoid. Hexadecadrol,Decaject,Decaject-L.A.,Decameth,Decaspray,Dexasone,Dexpak,Hexadrol,Maxidex,Methylfluorprednisolone,Millicorten,Oradexon,Decaject L.A.
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D051418 Focal Adhesion Kinase 2 A non-receptor protein-tyrosine kinase that is expressed primarily in the BRAIN; OSTEOBLASTS; and LYMPHOID CELLS. In the CENTRAL NERVOUS SYSTEM focal adhesion kinase 2 modulates ION CHANNEL function and MITOGEN-ACTIVATED PROTEIN KINASES activity. CADTK Protein,Calcium-Dependent Protein Tyrosine Kinase,Cell Adhesion Kinase Beta,FAK Autokinase,Focal Adhesion Kinase Autokinase,PYK2 Protein Tyrosine Kinase,Proline-Rich Tyrosine Kinase 2,Protein Tyrosine Kinase PYK2,RAFTK Protein,Related Adhesion Focal Tyrosine Kinase,Calcium Dependent Protein Tyrosine Kinase,Proline Rich Tyrosine Kinase 2

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