LIM domain protein, LPP, interacts via its C‐terminal LIM domain with the a‐actinin targeting protein, Palladin at focal adhesions

Lipoma preferred partner (LPP) is a proline‐rich LIM‐domain family protein highly expressed at cell surface dense bodies, focal adhesions, and nuclei in smooth muscle(SM) 1 . Palladin, an actin‐associated protein with proline‐rich motifs 2 was identified using the C terminal of LPP as bait in a yeast two hybrid system. Palladin colocalizes with α‐actinin along stress fibers, at focal adhesions and cell‐cell juctions 2 . In adult tissue, Palladin, like LPP, is highly expressed in SM 2 . The Palladin interacting region of LPP was mapped to the first and second LIM domains. N‐terminal Palladin interacted with LPP, but not solely through its FLPP and PPPP motifs, since the binding still existed after mutating these motifs. The specific interaction of Palladin with LPP was demonstrated both in vitro and in vivo. LPP and Palladin colocalized at focal adhesions. Both LPP and Palladin enhanced cell migration. LPP and Palladin expression was markedly decreased, unlike elevated vinculin or paxillin, in migration defective focal adhesion kinase (FAK) null cells. Overexpression of LPP and Palladin partially restored cell migration. Inducible expression of FAK in FAK null cells using a tetracyclin repression system can up‐regulate LPP, FAK, and Palladin. Taken together, we identified an interaction between one of the LIM protein family members, LPP, and the actin associated protein, Palladin. Both proteins localize to focal adhesions, increase cell motility, and their expression is FAK dependent. Supported by NIH P01 HL 19242