Cold Spring Harbor Laboratory

University of California

Sloan-kettering Institute for Cancer Research

Ryuji Kobayashi

Jasper D Rine

Bruce W Stillman

Ira Herskowitz

Joachim Li

Kimberly Gavin

Patricia Laurenson

Francis J McNally

Margit Foss

Stephen P Bell

Masumi Hidaka

Nicholas A Carpino

Bayard D Clarkson

Annabel O'c Strife

David G Wisniewski

Characteristic of chronic myelogenous leukemia (CML) is the presence of the chimeric p120.sup.bcr-abl protein possessing elevated protein tyrosine kinase activity relative to normal c-abl tyrosine kinase. Hematopoietic progenitors isolated from CML patients in the chronic phase contain a constitutively tyrosine phosphorylated protein that migrates at approximately 62 kDa by SDS-PAGE and associates with the p120 ras GTPase-activating protein (GAP). This novel protein, called p62.sup.dok (p62 protein downstream of tyrosine kinases), was isolated from a hematopoietic cell line expressing p120.sup.bcr-abl. Association of p62.sup.dok with GAP correlates with its tyrosine phosphorylation. p62.sup.dok is rapidly tyrosine phosphorylated upon activation of the c-kit receptor, implicating it as a component of a signal transduction pathway downstream of receptor tyrosine kinases.

Human gene/protein involved in chronic myelogenous leukemia

Origin of Replication Complex (ORC) genes, nucleic acids which encode ORC proteins and hybridization reagents, probes and primers capable of hybridizing with ORC genes and methods for screening chemical libraries for lead compounds for pharmacological agents useful in the diagnosis or treatment of disease associated undesirable cell growth are provided. An exemplary screen involves forming a mixture comprising a recombinant ORC protein, a natural intracellular ORC protein binding target, and a candidate pharmacological agent; incubating the mixture under conditions whereby, but for the presence of said candidate pharmacological agent, said ORC protein selectively binds said binding target; and detecting the presence or absence of specific binding of said ORC protein to said binding target.

Origin of replication complex genes

Origin of replication complex genes and methods of using the same

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Cold Spring Harbor, NY, United States of America

Ryuji Kobayashi