Open AccessAssociation of focal adhesion kinase with its potential substrate phosphatidylinositol 3-kinase.
Author(s) -
Hong Chen Chen,
Jun Guan
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.21.10148
Subject(s) - autophosphorylation , focal adhesion , microbiology and biotechnology , proto oncogene tyrosine protein kinase src , ptk2 , tyrosine kinase , phosphatidylinositol , tyrosine phosphorylation , biology , signal transduction , kinase , chemistry , mitogen activated protein kinase kinase , protein kinase a
The focal adhesion kinase (FAK) has been implicated in signal transduction pathways initiated by cell adhesion receptor integrins and by neuropeptide growth factors. To gain insight into FAK function, we examined the potential interaction of FAK with intracellular signaling molecules containing the Src homology 2 domains. We report here the stable association of FAK with phosphatidylinositol 3-kinase (PI3-kinase; EC 2.7.1.137) in NIH 3T3 mouse fibroblasts. This interaction was stimulated by cell adhesion concomitant with FAK activation. We also found that recombinant FAK bound to the p85 subunit of PI 3-kinase directly in vitro and that autophosphorylation of recombinant FAK in vitro increased its binding to PI 3-kinase. We detected increased tyrosine phosphorylation of the p85 subunit of PI 3-kinase during cell adhesion and observed direct phosphorylation of p85 by FAK in vitro. Together, these results suggest that PI 3-kinase may be a FAK substrate in vivo and serve as an effector of FAK.