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.

Yoshikazu Takada
Professor
Summary
Published articles Show More
Direct Binding of the EGF-like Domain of Neuregulin-1 to Integrins (alphavbeta3 and alpha6beta4) Is Involved in Neuregul...
Published in JBIC Journal of Biological Inorganic Chemistry
Identification of Equine Lactadherin-derived Peptides That Inhibit Rotavirus Infection via Integrin Receptor Competition...
Published in Journal of Biological Chemistry
Human rotavirus is the leading cause of severe gastroenteritis in infants and children under the age of 5 years in both developed and developing countries. Human lactadherin, a milk fat globule membrane glycoprotein, inhibits human rotavirus infection in vitro, whereas bovine lactadherin is not active. Moreover, it protects breastfed infants agains...
Proinflammatory secreted phospholipase A2 type IIA (sPLA-IIA) induces integrin activation through direct binding to a ne...
Published in Journal of Biological Chemistry
Integrins are activated by signaling from inside the cell (inside-out signaling) through global conformational changes of integrins. We recently discovered that fractalkine activates integrins in the absence of CX3CR1 through the direct binding of fractalkine to a ligand-binding site in the integrin headpiece (site 2) that is distinct from the clas...