Secreted growth hormones and cytokines signal between cells to regulate growth and differentiation as well as responses to injury and infection. Inappropriate growth control is a defining feature of human cancer while excessive cytokine responses underlie autoimmune and inflammatory diseases, such as rheumatoid arthritis, diabetes and asthma. Classically, growth factor binding to transmembrane receptors activates receptor (RTK) and non-receptor (PTK) protein tyrosine kinases to create intracellular docking sites for the recruitment of SH2 effector proteins (e.g. GRB2, STATs) leading to downstream signalling and transcription. Similarly, BMP/TGFβ-receptor serine kinases recruit SMAD MH2 domains for the control of stem cell fate and tissue morphogenesis.
Growth factor signalling is also tightly regulated by protein phosphatases and E3 ubiquitin ligases, which can limit the duration of signalling. In 1998, the HER-2-specific antibody Herceptin was launched against breast cancer and became the first approved treatment directed against a growth factor-dependent protein kinase. The further discovery of potent and selective Abl tyrosine kinase inhibitors, such as Gleevec, has raised considerable hope for further drug therapies. The SGC aims to advance these discoveries by addressing the structure, mechanism and druggability of growth factor signalling proteins, including protein kinases, phosphatases and E3 ubiquitin ligases.