The epidermal growth factor.
Epidermal growth factor (EGF) is a single polypeptide of 53 amino acid residues which is involved in the regulation of cell proliferation. Egf exerts its effects in the target cells by binding to the plasma membrane located EGF receptor. The EGF receptor is a transmembrane protein tyrosine kinase. Binding of EGF to the receptor causes activation of the kinase and subsequently receptor autophosphorylation. The autophosphorylation is essential for the interaction of the receptor with its substrates. These bind to the receptor by the so-called SH2 domains. The signal transduction pathways activated by EGF include the phosphatidylinositol pathway, leading to activation of protein kinase C and to increase in the intracellular Ca2+ concentration, and to the ras pathway leading to MAP kinase activation. Recently the cytoplasm has been implicated as playing an important role in EGF induced signal transduction. The EGF receptor has been demonstrated to be an actin-binding protein. In addition EGF causes a rapid actin depolymerisation and the formation of membrane ruffles. In particular these membrane ruffles have been shown to act as the first site of signal transduction after EGF binding, and thus may be considered as signal transduction structures. Finally evidence has been presented suggesting a positive role for EGF and/or the receptor in the nucleus.
Boonstra
J
J
Dept. Molecular Cell Biology, University Utrecht, The Netherlands.
Rijken
P
P
Humbel
B
B
Cremers
F
F
Verkleij
A
A
van Bergen en Henegouwen
P
P
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology; D002467:Cell Nucleus / Q000502:physiology; D002477:Cells / Q000166:cytology; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7; D003599:Cytoskeleton / Q000502:physiology; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*; D066246:ErbB Receptors / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008840:Microfilament Proteins / Q000502:physiology; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D015398:Signal Transduction; D018631:ras Proteins / Q000378:metabolism
D008840:Microfilament Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases; D018631:ras Proteins