The focal adhesion targeting sequence is the major inhibitory moiety of Fak-related non-kinase.
Focal adhesion kinase (FAK) plays an important role in integrin-mediated signal transduction pathways and its C-terminal noncatalytic domain Fak-related non-kinase (FRNK), which is autonomously expressed, acts as an inhibitor of FAK. A model has been proposed where FAK and FRNK compete for an essential common binding protein. A FRNK variant in which the direct interaction with v-Crk-associated tyrosine kinase substrate (CAS) was disturbed by point mutations still functioned as an inhibitor of FAK, suggesting that FRNK is unlikely to inhibit FAK by sequestering CAS. Deletion variants of FRNK within the region N-terminal to the focal adhesion targeting (FAT) sequence were still able to inhibit FAK function, indicating that this region is dispensable for the inhibitory effect of FRNK. Overexpression of a green fluorescent protein (GFP) fusion protein containing the FAT sequence delayed cell spreading and reduced FAK tyrosine phosphorylation. This indicates that the FAT sequence is the major inhibitory moiety within FRNK.
Mortier
E
E
Department of Biochemistry, Janssen Research Foundation, Turnhoutseweg 30, B-2340, Beerse, Belgium.
Cornelissen
F
F
van Hove
C
C
Dillen
L
L
Richardson
A
A
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002448:Cell Adhesion; D002478:Cells, Cultured; D002642:Chick Embryo; D051416:Focal Adhesion Protein-Tyrosine Kinases; D022001:Focal Adhesions / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D007091:Image Processing, Computer-Assisted; D007202:Indicators and Reagents / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017384:Sequence Deletion; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D007202:Indicators and Reagents; D008164:Luminescent Proteins; C099942:NEDD9 protein, human; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; C113183:FAK-related nonkinase; D011505:Protein-Tyrosine Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases