Biomaterial Database

Protein tyrosine kinase inhibition blocks granule exocytosis and cytolytic function of lymphokine-activated killer cells. 1996

M J Frederick, and T K Yu, and E G Krohn, and D A Johnston, and E A Grimm

Department of Tumor Biology, University of Texas 77030, USA.

Short-term pretreatment of human lymphokine-activated killer cells (LAK) with the protein tyrosine kinase-specific inhibitor Herbimycin A (Herb A) blocked cytotoxic function against the NK-resistant (LAK-sensitive) tumor targets, SK-Mel-1 (human melanoma) and Daudi (human lymphoma). Greater than 50% inhibition of LAK activity was observed after a 2.5-h pretreatment with 0.125 microgram/ml (ca. 0.2 microM) Herb A. Inhibition of LAK occurred over a time interval in which LAK were not dependent upon IL-2 for maintenance of killing function, supporting the conclusion that the drug interfered with mobilization of cytotoxic function. Conjugate formation between LAK and tumor targets was unaffected by Herb A, indicating that inhibition was occurring at a post-binding step. Granule exocytosis as measured by BLT-esterase release was detected from LAK after coincubation with tumor targets, and was inhibited by Herb A pretreatment. The majority of LAK killing was dependent upon extracellular calcium, supporting the hypothesis that granule exocytosis rather than Fas ligand was the principal pathway leading to target cell death. The data suggest that protein tyrosine kinases play a pivotal role in LAK cytolytic function by regulating granule exocytosis.

UI	MeSH Term	Description	Entries
D007376	Interleukin-2	A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.	IL-2,Lymphocyte Mitogenic Factor,T-Cell Growth Factor,TCGF,IL2,Interleukin II,Interleukine 2,RU 49637,RU-49637,Ro-23-6019,Ro-236019,T-Cell Stimulating Factor,Thymocyte Stimulating Factor,Interleukin 2,Mitogenic Factor, Lymphocyte,RU49637,Ro 23 6019,Ro 236019,Ro236019,T Cell Growth Factor,T Cell Stimulating Factor
D008024	Ligands	A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)	Ligand
D008562	Membrane Glycoproteins	Glycoproteins found on the membrane or surface of cells.	Cell Surface Glycoproteins,Surface Glycoproteins,Cell Surface Glycoprotein,Membrane Glycoprotein,Surface Glycoprotein,Glycoprotein, Cell Surface,Glycoprotein, Membrane,Glycoprotein, Surface,Glycoproteins, Cell Surface,Glycoproteins, Membrane,Glycoproteins, Surface,Surface Glycoprotein, Cell,Surface Glycoproteins, Cell
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
D011809	Quinones	Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.
D002449	Cell Aggregation	The phenomenon by which dissociated cells intermixed in vitro tend to group themselves with cells of their own type.	Aggregation, Cell,Aggregations, Cell,Cell Aggregations
D003594	Cytoplasmic Granules	Condensed areas of cellular material that may be bounded by a membrane.	Cytoplasmic Granule,Granule, Cytoplasmic,Granules, Cytoplasmic
D003602	Cytotoxicity, Immunologic	The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.	Tumoricidal Activity, Immunologic,Immunologic Cytotoxicity,Immunologic Tumoricidal Activities,Immunologic Tumoricidal Activity,Tumoricidal Activities, Immunologic
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D005089	Exocytosis	Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the CELL MEMBRANE.