УДК 577.112.7:576.32/36:616-006
D. DVORNIKOV 1,2, L. DROBOT2, M. J. REDOWICZ1 and S. HAVRYLOV1
TKS4 – NEW RUK/CIN85 INTERACTION PARTNER
1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine
2Nencki Institute of Experimental Biology, Polish Academy of Sciences
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Tks4 is a phox homology (PX) and Src homology 3 (SH3) domain-containing adaptor protein and a Src kinase substrate. In Src-transformed fibroblasts Tks4 supports formation of podosomes (Buschman et al., 2009) - actin-rich membrane protrusions that share many features with invadopodia of aggressive cancer cells. Proteolytic activities of either invadopodia and podosomes allow cells to degrade extracellular matrix and infiltrate surrounding tissues.
Now we have identified Tks4 as a novel interaction partner of Ruk/CIN85. Tks4 protein contains several potential consensus sequences for SH3 domains of Ruk/CIN85 and is effectively recruited by each of the three SH3 domains of this adaptor in vitro. Initial structure-function analysis indicates that the region of Tks4 responsible for interaction with Ruk/CIN85 is located between third SH3 domain and proline-rich region of this protein. In addition, partial colocalization between Tks4 and Ruk/CIN85 is revealed in HeLa cells.
By further experiments we plan to confirm biological significance of detected interaction between two studied proteins in vivo. Because Ruk/CIN85 is a crucial component of invadopodia (Nam et al., 2007) we speculate that Ruk/CIN85-Tks4 complex may function as a molecular platform required for biogenesis of these invasive structures and hence may serve an attractive target for anti-metastatic therapy.