Chiron Corporation

Cetus Corporation

Cold Spring Harbor Laboratory

Gail L Wong

Francis P McCormick

Robin Clark

Bonnee Rubinfeld

Danute E Nitecki

George A Martin

Norman Arnheim

Edward C O'Rourke

Kirston E Koths

Robert F Halenbeck

Paul G Polakis

James R Feramisco

Native Type II GAP (GTPase activating protein), its uses in cancer diagnosis, and methods for obtaining and purifying native and recombinant Types I and II GAPs are described.

Native type II GAP, methods for purifying various GAPs and uses of GAPs

The subject invention provides for nucleotide sequences encoding polypeptide p62 and derivatives thereof. Another aspect of the subject invention also provides for methods of purifying p62 and derivatives thereof from cells naturally producing p62 and from cells genetically modified so as to produce p62. The subject invention also provides for methods of assaying tyrosine kinase activity by means of measuring the phosphorylation of p62 and p62 derivatives. Measurement of p62/p62 derivative phosphorylation may be used to determine whether or not a call is cancerous.

Method for determining tyrosine kinase activity

Peptides, that inhibit GAP stimulated ras p21 hydrolysis of GTP; peptides that mediate dissociation of GDP from ras p21-GTP complex; and antibodies to the peptides are described. These peptides are useful as cancer diagnostics and therapeutics, particularly to detect cancer cells with an over expression of normal or oncogenic ras p21 protein and to treat cancer caused by ras oncogene. Methods for assaying products of oncogenes using the described peptides and antibodies are also disclosed. Method for treating cancer caused by ras oncogenes is also disclosed.

GTPase activating protein fragments

Guanosine triphosphatase activating protein (GAP) DNA sequences are described that are useful as cancer diagnostics, particularly to detect cancer cells that express the ras oncogene protein p21 by measuring the level of GAP gene expression or amplification.

Gap gene sequences

Nucleic acids encoding a gap-associated protein

Polypeptides and antibodies derived from GAP associated protein, p62

Antibodies exhibit specificity toward single amino acid differences between proteins. These antibodies may be produced by synthesizing a peptide of the appropriate amino acid sequence contained in the protein, immunizing a host with the peptide, and extracting sera from the host to obtain the antibodies. The antibodies and the desired protein are then immunoprecipitated under conditions of partial denaturation to expose the epitope of the protein. The antibodies may be used for diagnostic or therapeutic purposes.

Peptide antibodies and their use in detecting oncogene products

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La Jolla, CA, United States of America

Gail L Wong