Lipid rafts: resolution of the "fyn problem"?

Molecular Immunology
Dominik Filipp, Michael Julius

Abstract

While both lck and fyn are essential to generating the full sequelae of proximal signals emanating from the TcR/CD3 complex, thus far, modeling the temporal and spatial involvement of fyn has been problematic. The absence of a binding partner, analogous to the role of CD4 in targeting lck, commonalties of structure, common modes of activation and overlapping substrate specificities support the conclusion that many aspects of their roles may be redundant. Whether or how their functions are coordinated remains obscure. Recent experiments incorporating membrane partitioning towards resolving the distinct roles of lck and fyn in TcR/CD3 mediated cellular activation demonstrate that the membrane microdomains, termed lipid rafts, function to segregate the two kinases in unstimulated primary cells, and offers resolution in modeling their non-redundant contributions to the proximal TcR/CD3 signaling. Their activation, while interdependent, is temporally and spatially uncoupled. Lck activation is upstream of fyn activation. Moreover lck-dependent fyn activation is unidirectional, predicting the existence of distinct kinase specific regulatory mechanisms operating in lipid rafts. Thus, more than merely vehicles supporting protein concent...Continue Reading

Citations

Aug 3, 2004·Nature Reviews. Immunology·Václav HorejsíBurkhart Schraven
Jul 29, 2008·The Journal of Biological Chemistry·Dominik FilippMichael Julius
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