Yoshikazu Takada

Previous work of the PI in integrin biology.
Yoshikazu Takada, M.D., Ph.D. was involved in identifying and characterizing several of the â1 integrins (VLA proteins) in the 1980s. He cloned the α2, α3, and α4 subunits and identified collagen, laminin, and vascular cell adhesion molecule-1 as their respective ligands. Dr. Takada also performed structure-function studies of several integrins using site-directed mutagenesis, particularly in the putative ligand-binding sites of integrins. His results were consistent with the crystal structure of the integrin αvβ3-RGD complex and helped interpret the integrin structure. Dr. Takada currently focuses on integrin-growth factor crosstalk. His group discovered the direct binding of integrins to FGF1, and determined that this interaction plays a critical role in FGF signaling. Most recently, they discovered that IGF-1 (insulin-like growth factor-1) directly binds to integrins and this interaction is involved in IGF/IGF1R signaling. These findings suggest that direct integrin binding is involved in growth factor signaling. It has been well established that integrins are involved in growth factor signaling, since antagonists to integrins suppress growth factor signaling. Dr. Takada’s current model of growth factor-integrin crosstalk is that 1) integrins interact with extracellular matrix (ECM) and growth factors bind to growth factor receptors, and 2) two separate signals merge together inside the cells to induce intracellular signals. He proposes that direct integrin binding to growth factors (e.g., IGF, neuregulin and FGF) plays a role in the crosstalk.