Nck-2 interacts with focal adhesion kinase and modulates cell motility.
Nck-2 is a ubiquitously expressed adaptor protein comprising primarily three N-terminal SH3 domains and one C-terminal SH2 domain. We report here that Nck-2 interacts with focal adhesion kinase (FAK), a cytoplasmic protein tyrosine kinase critically involved in the cellular control of motility. Using a mutational strategy, we have found that the formation of the Nck-2-FAK complex is mediated by interactions involving multiple SH2 and SH3 domains of Nck-2. The Nck-2 SH2 domain-mediated interaction with FAK is dependent on phosphorylation of Tyr397, a site that is involved in the regulation of cell motility. A fraction of Nck-2 co-localizes with FAK at cell periphery in spreading cells. Furthermore, overexpression of Nck-2 modestly decreased cell motility, whereas overexpression of a mutant form of Nck-2 containing the SH2 domain but lacking the SH3 domains significantly promoted cell motility. These results identify a novel interaction between Nck-2 and FAK and suggest a role of Nck-2 in the modulation of cell motility.
Goicoechea
Silvia M
SM
Department of Pathology, University of Pittsburgh, 707B Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
Tu
Yizeng
Y
Hua
Yun
Y
Chen
Ka
K
Shen
Tang-Long
TL
Guan
Jun-Lin
JL
Wu
Chuanyue
C
D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D005353:Fibronectins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D046911:Macromolecular Substances; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000502:physiology*; D011554:Pseudopodia / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D018909:src Homology Domains
D002352:Carrier Proteins; D005353:Fibronectins; D046911:Macromolecular Substances; D011993:Recombinant Fusion Proteins; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human