Scaffolding by p85

Abstract

Two papers discuss the role of the p85 subunit of phosphoinositol 3 kinase (PI3K) that is independent of its role in activating the catalytic subunit of the kinase. González-García et al. showed that the p85 subunit was essential for assembling the ribosomal kinase p70S6K into a complex with the FKBP-12 rapamycin-associated protein (FRAP). This interaction promoted the persistent activation of the ribosomal kinase by inhibiting the dephosphorylation of the kinase by protein phosphatase 2A (PP2A). The impaired activation of p70S6K in the presence of the p85 mutant was blocked by inhibitors of PP2A or by expression of a FRAP-resistant mutant of p70S6K. The experiments with p70S6K and p85 were performed with mutants of p85 that were missing various protein interaction domains, although that did not disrupt the ability of p85 to interact with and to activate the PI3K catalytic subunit. The second paper showed that a mutant of p85 that was unable to interact with the PI3K catalytic subunit constitutively activated an interleukin-2 (IL-2) reporter gene in a transfected T cell hybridoma cell line. Dominant-negative mutants of the guanosine triphosphatase Rac or deletion of the Rac-binding BH domain of p85 inhibited transcriptional activation of the reporter gene. In T cells, a small amount of p85 was detected in a complex with Rac that did not include the catalytic PI3K subunit, suggesting that p85 may exist in separate signaling pools. Thus, p85 appears to serve multiple roles in signaling pathways and maybe should be considered a molecular adaptor rather than a subunit of PI3K (see the STKE Perspective by Okkenhaug and Vanhaesebroeck ). A. González-García, E. Garrido, C. Hernández, B. Alvarez, C. Jiménez, D. A. Cantrell, N. Pullen, A. C. Carrera, A new role for the p85-phosphatidylinositol 3-kinase regulatory subunit linking FRAP to p70 S6 kinase activation. J. Biol. Chem. 277 , 1500-1508 (2002). [Abstract] [Full Text] H. Kang, H. Schneider, C. E. Rudd, Phosphatidylinsositol 3-kinase p85 adaptor function in T-cells. J. Biol. Chem. 277 , 912-921 (2002). [Abstract] [Full Text] K. Okkenhaug, B. Vanhaesebroeck, New responsibilities for the PI3K regulatory subunit p85α. Science's STKE (2001), http://stke.sciencemag.org/cgi/content/full/OC_sigtrans;2001/65/pe1. [Abstract] [Full Text]