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Disclosed are human mitogen-activated (MAP) kinase kinase isoforms (MKKs). MKKs mediate unique signal transduction pathways that activate human MAP kinases p38 and JNK, which result in activation of other factors, including activating transcription factor-2 (ATF2) and c-Jun. The pathways are activated by a number of factors, including cytokines and environmental stress. Methods are provided for identifying reagents that modulate MKK function or activity and for the use of such reagents in the treatment of MKK-mediated disorders.

Titel:	Cytokine-, stress-, and oncoprotein-activated human protein kinase kinases
Autor/in / Beteiligte Person:	Davis, Roger ; Raingeaud, Joel ; Derijard, Benoit
Link:	View record in USPTO Patent Grants (Volltext)
Veröffentlichung:	1998
Medientyp:	Patent
Sonstiges:	Nachgewiesen in: USPTO Patent Grants Sprachen: English Patent Number: 5,804,427 Publication Date: September 08, 1998 Appl. No: 08/446,083 Application Filed: May 19, 1995 Assignees: University of Massachusetts (Boston, MA) Claim: We claim Claim: 1. A substantially pure human mitogen-activated protein kinase kinase (MKK) polypeptide having serine, threonine, and tyrosine kinase activity, wherein said MKK polypeptide phosphorylates human mitogen-activated protein (MAP) kinase p38, has a molecular weight of about 36 kD, and is encoded by a nucleic acid sequence that hybridizes under stringent conditions to a sequence fully complementary to the nucleic acid sequence of GenBank accession number L36719. Claim: 2. A polypeptide of claim 1 comprising the amino acid sequence of SEQ ID NO:2. Claim: 3. A substantially pure human mitogen-activated protein kinase kinase (MKK) polypeptide having serine, threonine, and tyrosine kinase activity, wherein said MKK polypeptide phosphorylates human mitogen-activated protein (MAP) kinase p38 and human c-Jun amino-terminal kinase (JNK), has a molecular weight of about 44 kD, and is encoded by a nucleic acid sequence that hybridizes under stringent conditions to a sequence fully complementary to the nucleic acid sequence of GenBank accession number L36870. Claim: 4. A polypeptide of claim 3 comprising the amino acid sequence of SEQ ID NO:1. Current U.S. Class: 435/194; 435/183; 530/350 Current International Class: C12N 912; C12N 900; C07K 100 Other References: Davis, Elsevier Science Ltd., TIBS 19:470-473, (1994). ; Derijard et al., Science, 267:682-685, (1995). ; Freshney et al., Cell, 78:1039-1049, (1994). ; Galcheva-Gargova et al., Science, 265:806-808, (1994). ; Gupta et al., Science, 267:389-393, (1995). ; Lin et al., Science, 268:286-290, (1995). ; Minden et al., Science, 266:1719-1723, (1994). ; Raingeaud et al., The Journal of Biological Chemistry, 270:7420-7426, (1995). ; Rouse et al., Cell, 78:1027-1037, (1994). ; Sanchez et al., Nature, 372:794-798, (1994). ; Whitmarsh et al., Science, 269:403-407, (1995). ; Xia et al., Science, 270:1326-1331, (1995). ; Yan et al., Nature, 372:798-800, (1994). ; Yashar et al., Molecular and Cellular Biology, 13:5738-5748, (1993). Primary Examiner: Sisson, Bradley L. Attorney, Agent or Firm: Fish & Richardson P.C.

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Cytokine-, stress-, and oncoprotein-activated human protein kinase kinases