CD16-mediated activation of phosphatidylinositol-3 kinase (PI-3K) in human NK cells involves tyrosine phosphorylation of Cbl and its association with Grb2, Shc, pp36 and p85 PI-3K subunit

Cristina Cerboni, Angela Gismondi, Gabriella Palmieri, Mario Piccoli, Luigi Frati, Angela Santoni

Research output: Contribution to journalArticle


Phosphatidylinositol 3-kinase (PI-3K) plays a key role in several cellular processes, including mitogenesis, apoptosis, actin reorganization and vesicular trafficking. The molecular events involved in its activation have not been fully elucidated and several reports indicate that a key event for enzyme activation is the interaction of the SH2 domains of the p85 regulatory subunit of PI-3K with tyrosine-phosphorylated proteins. In this study, we investigated the involvement of the product of the proto-oncogene c-Cbl in the activation of PI-3K triggered by CD16 in human NK cells and the possible mechanisms leading to PI-3K recruitment to the plasma membrane. Our results indicate that stimulation of NK cells through CD16 results in a rapid tyrosine phosphorylation of Cbl, which is constitutively associated with Grb2 and forms an activation-dependent complex with the p85 subunit of PI-3K. In addition, we detected the presence of the Grb2-associated tyrosine-phosphorylated p36 and Shc proteins in anti-Cbl and anti-p85 immunoprecipitates from CD16-stimulated NK cell lysates. Upon CD16 stimulation, PI-3K activity was found associated with Cbl and to a lesser extent with Grb2 and Shc as well as with the ζ chain of the CD16 receptor complex. Overall these results suggest that the formation of a complex containing either Shc or pp36 associated with Grb2, Cbl and the p85 subunit of PI-3K is one of the major mechanisms which might couple CD16 to the PI-3K pathway in NK cells.

Original languageEnglish
Pages (from-to)1005-1015
Number of pages11
JournalEuropean Journal of Immunology
Issue number3
Publication statusPublished - Mar 1998



  • Fc receptor
  • Human
  • NK cell
  • Signal transduction

ASJC Scopus subject areas

  • Immunology

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