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PMID: 7937853 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Association of focal adhesion kinase with its potential substrate phosphatidylinositol 3-kinase.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 91 ·No. 21 ·1994-10-11 ·Pages 10148-52

Chen HC, Guan JL

Abstract

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.

MeSH Terms
3T3 Cells Animals Blotting, Western Cell Adhesion Molecules/biosynthesis,isolation & purification,metabolism Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases Glutathione Transferase/biosynthesis Macromolecular Substances Mice Phosphatidylinositol 3-Kinases Phosphotransferases (Alcohol Group Acceptor)/isolation & purification,metabolism Protein Binding Protein-Tyrosine Kinases/biosynthesis,isolation & purification,metabolism Recombinant Fusion Proteins/biosynthesis,isolation & purification,metabolism Recombinant Proteins/biosynthesis,isolation & purification,metabolism Substrate Specificity Transfection
Chemicals
Cell Adhesion Molecules Macromolecular Substances Recombinant Fusion Proteins Recombinant Proteins Glutathione Transferase Phosphatidylinositol 3-Kinases Phosphotransferases (Alcohol Group Acceptor) Protein-Tyrosine Kinases Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases Ptk2 protein, mouse
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Chen H C
Department of Pathology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
Guan J L
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29 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.91.21.10148
Published
1994-10-11
Pages
10148-52
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC44975
Subset
IM
Grants
NIGMS NIH HHS · R01GM48050 · United States
External Links
PubMed source DOI: 10.1073/pnas.91.21.10148 PMC Full Text View journal details
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