¹Division of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan

²Division of Cell Cycle Regulation, Cancer Research Institute, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan

³Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, MD 20892-4370, USA

Correspondence to: T Takino, E-mail: ttakino@kenroku.kanazawa-u.ac.jp

Focal adhesion kinase (FAK) becomes activated and tyrosine-phosphorylated in response to cell adhesion to extracellular matrix proteins in a variety of cell types, and associates with a number of signaling molecules, structural proteins, and integrin cytoplasmic domains. Here we demonstrated that c-Jun N-terminal kinase (JNK)/stress activated protein kinase-associated protein 1 (JSAP1), a scaffold factor in the mitogen-activated protein kinase (MAPK) cascades, forms a complex with the N-terminus of FAK. The complex formation was further stimulated by c-Src, in which JSAP1 was tyrosine-phosphorylated and other FAK/Src signaling molecules were recruited. Fibronectin (FN) stimulation of cells expressing JSAP1 induced its tyrosine phosphorylation concomitant with association with FAK. Expression of JSAP1 in Hela cells facilitated formation of well-organized focal contacts and actin stress fibers, and promoted cell spreading onto FN. Taken together, these results suggest that JSAP1 is involved an integrin-mediated signaling pathway through FAK/Src by recruiting other signaling molecules, resulting in promotion of cell spreading onto FN.

Oncogene (2002) 21, 6488-6497. doi:10.1038/sj.onc.1205840

FAK; JSAP1; Src; tyrosine phosphorylation