TGF-alpha

Transforming Growth Factor-&alpha (TGF-alpha was originally isolated from the conditioned media of oncogenically-transformed cells as an EGF-like bioactivity. TGF-alpha is a member of the EGF family of cytokines that are synthesized as transmembrane precursors and are characterized by the presence of one or several EGF structural units in their extracellular domain. The soluble forms of these cytokines are released from the transmembrane protein by proteolytic cleavage. Membrane-bound proTGF-alpha is biologically active and seems to play a role in mediation of cell-cell adhesion and in juxtacrine stimulation of adjacent cells. Expression of TGF-alpha is widespread in tumors and transformed cells. TGF-alpha is also expressed in normal tissues during embryogenesis and in adult tissues, including pituitary, brain, keratinocytes and macrophages. Mature TGF-alpha shows approximately 93% amino acid sequence identity with mouse or rat TGF-alpha and is not species-specific in its biological effects. TGF-α binds to the EGF receptor and activates the receptor tyrosine kinase. Accordingly, TGF-alpha shows a similar potency to EGF as a mitogen for fibroblasts and as an inducer of epithelial development in vivo. TGF-alpha is reportedly more potent than EGF as an angiogenic factor in vivo and as a stimulator for keratinocyte migration. The EGF receptor gene represents the cellular homologue of the avian v-erb-B oncogene.