Src-family kinases: rheostats of immune cell signaling.

In immune cells, Src-family kinases have been implicated as critical regulators of a large number of intracellular signaling pathways. Studies of gene knockout mice lacking various family members have both confirmed the requirement for these kinases in some pathways and provided surprising insight into their roles in other pathways. In many cases, loss of a single kinase produces only a modest/moderate defect in the pathway being studied, while combinatorial mutants have more profound defects. In several cases, loss of Src-family kinase activity results in activation of signaling, illuminating the fact that these molecules play important roles in inhibitory signaling. This review will focus on both the positive and negative roles these kinases play in immunoreceptor and integrin signaling pathways. The overall observation that these molecules play such diverse signaling functions leads one to the conclusion that this family of proteins serves as general modulators of immune cell signaling.