PROTONCOGENES
, Protooncogenes Type of mechanism Protein Oncogenic mutation Remarks
Positive acting growth Chromosomal Platel derived growth Chromosomal translocation in Sis-oncogene encodes a specific type of PDGF that can
factors. translocation factor (PDGF). which a part of the sis gene is auto stimulate proliferation of cells that normally express
joined to a part of gene PDGF receptor (Autocrine stimulation).
encoding collagen. Normally, cells are only stimulated by PDGF when it is
released from the neighbouring cells (Paracrine
stimulation).
The chromosomal translocation of a part of sis oncogene to
collagen gene results in uncontrollable expression of PDGF.
Growth factor receptors. Point mutation Her2 receptor Point mutation resulting in Her2 receptor when has a valine to glutamine point
Neu oncoprotein substitution of valine to mutation results in permanent dimerization of Her2
(When Her2 glutamine in the transmembrane receptors. This dimerization constitutively activates the
becomes oncogenic) region. pathway associated with the Her2 receptor. This results in
uncontrolled cell proliferation.
Local DNA EGF receptor. Deletion of N terminal of EGF Truncation of N termini of EGF receptor results in
rearrangements (DNA ErbB oncoprotein. receptor. permanent dimerization of EGF receptor and thus
deletion). (When EGF constitutively activating pathways associated with it. This
becomes oncogenic). results in uncontrolled cell proliferation.
Local DNA TRK oncogene. DNA inversion between two This inversion leads to formation of a fusion protein
rearrangements (DNA genes, NTRK1 (a tyrosine containing tyrosine kinase site of receptor region joined to
inversion). receptor kinase) and TPM3 tropomyosin molecule.
(Non muscle tropomyosin). This results in formation of a coiled structure which causes
dimerization of two polypeptides. This permanent
dimerization of fusion protein results in permanent
activation of tyrosine kinase.
Signal transduction Point mutation. Ras oncogene. Any point mutation that converts Creates hyperactive forms of Ras protein – Constitutive
proteins. glycine amino acid at position expression of MPAK/Ras pathway – Increased cell
12 into any other amino acid. proliferation.
These are one of the first non-viral oncogenes.
Non-receptor protein Src gene product is pp60 and is bound to plasma
tyrosine kinase – membrane by its N-terminus myristate residue.
Src. It is a type of cytosolic non-receptor tyrosine kinase
originally identified in the Rous sarcoma virus.
Normally, src leads to activation of multiple pathways
(JAK/STAT, PI3K, MAPK/Ras, JNK etc) which leads to cell
survival, angiogenesis, proliferation and cell motility and
migration.
, Protooncogenes Type of mechanism Protein Oncogenic mutation Remarks
Positive acting growth Chromosomal Platel derived growth Chromosomal translocation in Sis-oncogene encodes a specific type of PDGF that can
factors. translocation factor (PDGF). which a part of the sis gene is auto stimulate proliferation of cells that normally express
joined to a part of gene PDGF receptor (Autocrine stimulation).
encoding collagen. Normally, cells are only stimulated by PDGF when it is
released from the neighbouring cells (Paracrine
stimulation).
The chromosomal translocation of a part of sis oncogene to
collagen gene results in uncontrollable expression of PDGF.
Growth factor receptors. Point mutation Her2 receptor Point mutation resulting in Her2 receptor when has a valine to glutamine point
Neu oncoprotein substitution of valine to mutation results in permanent dimerization of Her2
(When Her2 glutamine in the transmembrane receptors. This dimerization constitutively activates the
becomes oncogenic) region. pathway associated with the Her2 receptor. This results in
uncontrolled cell proliferation.
Local DNA EGF receptor. Deletion of N terminal of EGF Truncation of N termini of EGF receptor results in
rearrangements (DNA ErbB oncoprotein. receptor. permanent dimerization of EGF receptor and thus
deletion). (When EGF constitutively activating pathways associated with it. This
becomes oncogenic). results in uncontrolled cell proliferation.
Local DNA TRK oncogene. DNA inversion between two This inversion leads to formation of a fusion protein
rearrangements (DNA genes, NTRK1 (a tyrosine containing tyrosine kinase site of receptor region joined to
inversion). receptor kinase) and TPM3 tropomyosin molecule.
(Non muscle tropomyosin). This results in formation of a coiled structure which causes
dimerization of two polypeptides. This permanent
dimerization of fusion protein results in permanent
activation of tyrosine kinase.
Signal transduction Point mutation. Ras oncogene. Any point mutation that converts Creates hyperactive forms of Ras protein – Constitutive
proteins. glycine amino acid at position expression of MPAK/Ras pathway – Increased cell
12 into any other amino acid. proliferation.
These are one of the first non-viral oncogenes.
Non-receptor protein Src gene product is pp60 and is bound to plasma
tyrosine kinase – membrane by its N-terminus myristate residue.
Src. It is a type of cytosolic non-receptor tyrosine kinase
originally identified in the Rous sarcoma virus.
Normally, src leads to activation of multiple pathways
(JAK/STAT, PI3K, MAPK/Ras, JNK etc) which leads to cell
survival, angiogenesis, proliferation and cell motility and
migration.
