National Jewish Center for Immunology and Respiratory Medicine

National Jewish Medical and Research Center

Gary L Johnson

Erwin W Gelfand

Isolated nucleic acid molecules encoding human MEKK proteins, and isolated MEKK proteins, are provided. The invention further provides antisense nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced and non-human transgenic animals carrying a human MEKK transgene. The invention further provides human MEKK fusion proteins and anti-human MEKK antibodies. Methods of using the human MEKK proteins and nucleic acid molecules of the invention are also disclosed, including methods for detecting human MEKK activity in a biological sample, methods of modulating human MEKK activity in a cell, and methods for identifying agents that modulate the activity of human MEKK.

Human MEKK proteins, corresponding nucleic acid molecules, and uses therefor

A method useful for regulating cytokine production by a hematopoietic cell by regulating an MEKK/JNKK-contingent signal transduction pathway in such a cell is disclosed. Methods of identifying compounds capable of specifically regulating an MEKK/JNKK-contingent signal transduction pathway in hematopoietic cells, a kit for identifying cytokine regulators, methods to treat diseases involving cytokine production, and cells useful in such methods are also set forth.

Regulation of cytokine production in a hematopoietic cell

The present invention relates to isolated MEKK proteins, nucleic acid molecules having sequences that encode such proteins, and antibodies raised against such proteins. The present invention also includes methods to use such proteins to regulate signal transduction in a cell. The present invention also includes therapeutic compositions comprising such proteins or nucleic acid molecules that encode such proteins and their use to treat animals having medical disorders including cancer, inflammation, neurological disorders, autoimmune diseases, allergic reactions, and hormone-related diseases. When MEKK is expressed, it phosphorylates and activates MKKs 1-4 (also referred to as MEK-1, MEK-2 and JNKK1 and JNKK2).

Method and product for regulating cell responsiveness to external signals

Isolated nucleic acid molecules encoding human MEKK proteins, and isolated MEKK proteins, are provided. The invention further provides antisense nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced and nonhuman transgenic animals carrying a human MEKK transgene. The invention further provides human MEKK fusion proteins and anti-human MEKK antibodies. Methods of using the human MEKK proteins and nucleic acid molecules of the invention are also disclosed, including methods for detecting human MEKK activity in a biological sample, methods of modulating human MEKK activity in a cell, and methods for identifying agents that modulate the activity of human MEKK.

The present invention relates to methods useful for identifying compounds capable of specifically controlling CD40 regulation of JNK or p38 activity useful for inhibiting immunoglobulin heavy chain class switching, cytokine production and activation of cells involved in an inflammatory response. The present invention also includes kits to perform such assays and methods to control disease related to such responses.

Method to regulate CD40 signaling

The present invention relates to isolated MEKK proteins, nucleic acid molecules having sequences that encode such proteins, and antibodies raised against such proteins. The present invention also includes methods to use such proteins to regulate signal transduction in a cell. The present invention also includes therapeutic compositions comprising such proteins or nucleic acid molecules that encode such proteins and their use to treat animals having medical disorders including cancer, inflammation, neurological disorders, autoimmune diseases, allergic reactions, and hormone-related diseases. When MEKK is expressed, it phosphorylates and activates MEKs including MEK-1, MEK-2 and JEK.

MEKK proteins

Methods for regulating MEKK protein activity

MEKK-related signal transduction kinases

The present invention relates to methods useful for identifying compounds capable of specifically regulating actin polymerization, stress fiber formation or focal adhesion assembly by regulating G.sub..alpha.12 and/or G.sub..alpha.13 activity in cells involved in inflammatory responses, immune responses, allergic responses and neuronal responses, kits to perform such assays and methods to control disease related to such responses.

Product and process to regulate actin polymerization

The present invention relates to isolated MEKK proteins, nucleic acid molecules having sequences that encode such proteins, and antibodies raised against such proteins. The present invention also includes methods useful for identifying compounds capable of specifically regulating signal transduction in cells expressing MEKK protein.

Mitogen ERK kinase kinase (MEKK) assay

The isolated nucleic acid sequence for MEKK, the MEKK amino acid sequence and protein, antibodies to MEKK, and methods for using such sequences, proteins and antibodies are described. The amino acid sequence of MEKK (MEK kinase), was elucidated from a cDNA sequence encoding a protein of 672 amino acid residues (73 kilodaltons). When MEKK is expressed, it phosphorylates and activates MEK. Phosphorylation and activation of MEK by MEKK is independent of Raf, a growth factor regulated protein kinase that also phosphorylates MEK. Thus, MEKK and Raf converge at MEK in the protein kinase network mediating the activation of MAPKs by hormones, growth factors, and neurotransmitters.

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Boulder, CO, United States of America

Gary L Johnson