How insulin signals globally and acts locally

Insulin stimulation in adipocytes sends signals through two pathways, one dependent on phosphatidylinositol-3-kinase (PI3K) and the other acting through the small membrane-associated GTPase TC10. On page 279, Kanzaki et al. reveal an unexpected convergence of the two pathways, and show that the localization of atypical protein kinase C (PKCζ/λ) to specific lipid raft microdomains confers specificity on the system.

Previous work had suggested that PI3K could activate PKCζ/λ or protein kinase B, but the relative importance of these downstream effectors was controversial. In the new study, the authors found that both the PI3K and TC10 pathways can activate PKCζ/λ in adipocytes, but only the TC10 pathway recruits PKCζ/λ to TC10-containing lipid raft microdomains. The localization is directed by Par6 and Par3, proteins that are known to link GTPases to PKCs in the worm C. elegans...