Membrane recruitment of scaffold proteins drives specific signaling. This study uses mathematical modelling to examine possible functions of scaffold proteins and identifies important variables that might alter these functions. Scaffold proteins confer diverse regulatory properties to protein kinase cascades. Cutting Edge: A-kinase anchor proteins are involved in maintaining resting T cells in an inactive state. AKAP signalling complexes: focal points in space and time. Signal transduction: hanging on a scaffold. What do scaffold proteins really do? Sci. Scaffold proteins may biphasically affect the levels of mitogen-activated protein kinase signaling and reduce its threshold properties. Neurabin: a novel neural tissue-specific actin filament-binding protein involved in neurite formation. Scaffolds, adaptors and linkers of TCR signaling: theory and practice. Activation of T lymphocytes and the role of the adapter LAT. Signalling pathways of the TNF superfamily: a double-edged sword. Signal transduction by the TCR for antigen. Platelet-derived growth factor receptor-mediated signal transduction from endosomes. Internalization of inactive EGF receptor into endosomes and the subsequent activation of endosome-associated EGF receptors. Similar effects of platelet-derived growth factor and epidermal growth factor on the phosphorylation of tyrosine in cellular proteins. It is probable that new tools, in addition to classic biochemical approaches, will be required to elucidate these functions.Ĭooper, J. The function and regulation of scaffold proteins is complex and much remains to be defined. In immune cells, scaffold proteins have an important role in the regulation of mitogen-activated protein kinase activation, calcium signalling, signalling downstream of innate immune receptors and cell polarity. Scaffolds can generate complex behaviours that include transient or sustained signalling, and oscillatory signalling, as well as provide positive and negative feedback. Initial studies of scaffold proteins indicate that they are important for spatial localization and amplification of signal transduction. This Review provides an overview of the numerous functions that have been attributed to scaffold proteins, and discusses various cytoplasmic scaffold proteins that are important in immune cells.Īlthough little is known about the exact role of scaffold proteins, mathematical modelling and engineered scaffold proteins have greatly enhanced our knowledge of their function. Scaffold proteins have an important role in regulating immune-cell signalling.