Insights into the physiology of TGF alpha and signaling through the EGF receptor revealed by gene targeting and acts of nature.
Transforming growth factor alpha (TGF alpha) is one of a group of structurally-related growth factors (the epidermal growth factor family of ligands) that interact with one or other members of the epidermal growth factor family of protein tyrosine kinase receptors (EGF-R's). A number of excellent reviews detailing our knowledge of this area have been recently published (Carpenter and Wahl, 1991; Derynck, 1992; Prigent and Lemoine, 1992). Rather than add to their number, this review focuses on new insights into the importance of TGF alpha and signaling through the EGF receptor considered in the context of the laboratory mouse. The new information has emerged from analysis of mutant mice generated either by classical gene targeting in embryonic stem (ES) cells or by accidents of nature. In addition to their intrinsic interest, these mice are proving invaluable in determining the importance of EGF receptor signaling in wound healing and as a contributing factor in the conversion of a normal cell into its tumorigenic counterpart.
Dunn
A R
AR
Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Victoria, Australia.
Mann
G B
GB
Fowler
K J
KJ
Grail
D
D
Hibbs
M L
ML
Alexander
W S
WS
Walker
F
F
Burgess
A W
AW
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002471:Cell Transformation, Neoplastic; D003043:Cocarcinogenesis; D004815:Epidermal Growth Factor / Q000502:physiology; D066246:ErbB Receptors / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D018390:Gene Targeting; D006197:Hair / Q000254:growth & development; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D005810:Multigene Family; D016254:Mutagenesis, Insertional; D010212:Papilloma / Q000139:chemically induced / Q000503:physiopathology; D011995:Recombination, Genetic; D015398:Signal Transduction / Q000502:physiology*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000503:physiopathology; D016211:Transforming Growth Factor alpha / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014738:Vibrissae / Q000254:growth & development; D014945:Wound Healing / Q000502:physiology
D016211:Transforming Growth Factor alpha; D015127:9,10-Dimethyl-1,2-benzanthracene; D004815:Epidermal Growth Factor; D066246:ErbB Receptors