PRINCIPLES OF TOXICOLOGY - Biology East Borneo

282 CHEMICAL CARCINOGENESISTABLE 13.5 Selected Protooncogenes and the Functions of Their Encoded ProteinsOncogene NameFunctionsisint-2tgf-αerbBfmskitmetH,N,K-rassrcyesablfesrafmosmycfosjunetsGrowth Factors aPlatelet-derived growth factorFibroblast growth factorTransforming growth factor-αGrowth Factor Receptors bEpidermal growth factor receptor (tyrosine kinase)Colony stimulating factor receptor (tyrosine kinase)Stem cell receptor (tyrosine kinase)Hepatocyte growth factor receptor (tyrosine kinase)GTP Binding Proteins (G proteins) cMembrane-associated GTP binding/GTPaseNonreceptor Tyrosine Kinases dMembrane associated—mediates integrin signalingMembrane associatedCytoplasmic with nuclear translocation ability—DNA binding and DNA transcriptionactivationCytoplasmicCytoplasmic Serine/Threonine Kinases ePhosphorylates MAPKK proteins in cell signalingActivates and/or stabilizes maturation promoting factor (MPF)Nuclear Transcription Factors fSequence-specific DNA binding protein (transcription factor)Combines with jun to form AP1 transcription factorCombines with fos to form AP1 transcription factorTranscription factora These are secreted factors that typically act in an autocrine or paracrine fashion.b Normally these receptors are transiently activated by ligand binding. Mutant forms are persistently activated.c Numerous growth factor receptors normally signal through GTP binding proteins. These proteins transiently activated in responseto ligand binding at the receptor. Mutant forms are persistently activated.d These are cytoplasmic proteins involved in the relay of signals from growth factor receptors and from the extracellular matrixthrough cytoskeletal proteins. Activation requires differential, transient phosphorylation of tyrosine residues. Mutant forms arepersistently activated.e These are another group of cytoplasmic proteins involved in the relay of signals to the cell nucleus. Activation requires differential,transient phosphorylation at serine and threonine residues. Mutant forms are persistently activated.f These proteins are localized primarily to the cell nucleus; where they function to transcriptionally activate and repress genesassociated with cell growth and differentiation.