SRC, proto-oncogene tyrosine-protein kinase

by Jennifer McDowall

to view SRC structure

Src-induced signaling from membrane/adhesions that controls cell behaviour

Reprinted from Biochim Biophys Acta 1602(2), M. Frame, Src in Cancer, 114-130, 2002, with permission from Elsevier, PMID: 12020799

The move from single-celled organisms to multi-cellular ones brought with it a need to co-ordinate a multitude of processes. No longer was a cell self-sufficient; cells took on specific roles that enabled them to perform tasks more efficiently, but at the cost that they were now dependent upon the products of other cells for their survival. The needs of different cell types differ dramatically according to their function and stage of development. Multi-cellular organisms had to develop complex systems of control in order to regulate the different processes going on in different cells at different times. This control must involve sophisticated communication to co-ordinate the multitude of processes if the organism is to function properly. Src is one of the many proteins involved in a highly complex, interconnected system of communication and control.

Src, a key regulator

Src is a non-receptor protein tyrosine kinase that plays a multitude of roles in cell signalling. Src is involved in the control of many functions, including cell adhesion, growth, movement and differentiation. Src is widely expressed in many cell types, and can have different locations within a cell. It appears that the subcellular location of Src can affect its function. Src can associate with cellular membranes, such as the plasma membrane, the perinuclear membrane and the endosomal membrane. At the plasma membrane, Src can transduce signals from a variety of receptors to internal signalling pathways that convey these signals to the nucleus, cytoskeleton and other cellular components. For example, Src can act through the growth factor receptors to affect cell growth and proliferation. Within the nucleus, Src is thought to help regulate the cell cycle and cell division by its interactions with other proteins. For example, Src can interact with Sam68 to help regulate gene expression. In bone osteoclasts, Src acts to regulate the respiratory enzyme cytochrome C oxidase (Cox), where Src-induced phosphorylation of Cox is required for maintaining high levels of ATP to meet the cells’ high energy requirements. Src can also be found in the cytoplasm, and between cells at adherens junctions, where it takes on different roles.

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