Ras regulatory interactions: novel targets for anti-cancer intervention?
Advances in the understanding of Ras oncoprotein function suggest novel points for anti-tumor intervention. First, upstream-acting guanine nucleotide exchange factors and SH2/SH3 domain-containing adaptor proteins that link Ras with growth factor receptor tyrosine kinases have recently been characterized. Second, work on downstream-acting Ras effector functions including the Ras GTPase-activating protein (p120GAP) and the Raf kinase has revealed direct biochemical interactions that are functionally required for oncogenic Ras signalling. We summarize progress in these areas and discuss the potential for novel applications to anti-cancer chemotherapy.
Prendergast
G C
GC
Department of Cancer Research, Merck Research Laboratories, West Point, PA 19486.
Gibbs
J B
JB
D019883:Alkyl and Aryl Transferases; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D051231:Farnesyltranstransferase; D020690:GTPase-Activating Proteins; D011905:Genes, ras; D006801:Humans; D008954:Models, Biological; D009857:Oncogenes; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf; D016283:Proto-Oncogene Proteins p21(ras) / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D014166:Transferases / Q000037:antagonists & inhibitors; D020703:ras GTPase-Activating Proteins
D000970:Antineoplastic Agents; D020690:GTPase-Activating Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D020703:ras GTPase-Activating Proteins; D014166:Transferases; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)