PRINCIPLES OF TOXICOLOGY

282 CHEMICAL CARCINOGENESIS
TABLE 13.5 Selected Protooncogenes and the Functions of Their Encoded Proteins
Oncogene Name Function
sis Platelet-derived growth factor
int-2 Fibroblast growth factor
tgf-α Transforming growth factor-α
Growth Factors a
Growth Factor Receptors b
erbB Epidermal growth factor receptor (tyrosine kinase)
fms Colony stimulating factor receptor (tyrosine kinase)
kit Stem cell receptor (tyrosine kinase)
met Hepatocyte growth factor receptor (tyrosine kinase)
GTP Binding Proteins (G proteins) c
H,N,K-ras Membrane-associated GTP binding/GTPase
Nonreceptor Tyrosine Kinases d
src Membrane associated—mediates integrin signaling
yes Membrane associated
abl Cytoplasmic with nuclear translocation ability—DNA binding and DNA transcription
activation
fes Cytoplasmic
Cytoplasmic Serine/Threonine Kinases e
raf Phosphorylates MAPKK proteins in cell signaling
mos Activates and/or stabilizes maturation promoting factor (MPF)
Nuclear Transcription Factors f
myc Sequence-specific DNA binding protein (transcription factor)
fos Combines with jun to form AP1 transcription factor
jun Combines with fos to form AP1 transcription factor
ets Transcription factor
a
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 response
to 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 matrix
through cytoskeletal proteins. Activation requires differential, transient phosphorylation of tyrosine residues. Mutant forms are
persistently 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 genes
associated with cell growth and differentiation.