1 research outputs found
Structural Basis for the Interaction between Pyk2-FAT Domain and Leupaxin LD Repeats
Proline-rich
tyrosine kinase 2 (Pyk2) is a nonreceptor tyrosine
kinase and belongs to the focal adhesion kinase (FAK) family. Like
FAK, the C-terminal focal adhesion-targeting (FAT) domain of Pyk2
binds to paxillin, a scaffold protein in focal adhesions; however,
the interaction between the FAT domain of Pyk2 and paxillin is dynamic
and unstable. Leupaxin is another member in the paxillin family and
was suggested to be the native binding partner of Pyk2; Pyk2 gene
expression is strongly correlated with that of leupaxin in many tissues
including primary breast cancer. Here, we report that leupaxin interacts
with Pyk2-FAT. Leupaxin has four leucine–aspartate (LD) motifs.
The first and third LD motifs of leupaxin preferably target the two
LD-binding sites on the Pyk2-FAT domain, respectively. Moreover, the
full-length leupaxin binds to Pyk2-FAT as a stable one-to-one complex.
Together, we propose that there is an underlying selectivity between
leupaxin and paxillin for Pyk2, which may influence the differing
behavior of the two proteins at focal adhesion sites