Role of Integrin-mediated Signal Transduction in Cell Growth and Differentiation

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(1) Alternative splicing of the fibronectin pre-nRNA at the EDA region was found to regulate the cell-adhesive and integrin alpha5beta1 binding activities of fibronectin. This is the first evidence for the regulation of the integrin-mediated signal transduction by alternative splicing of the extracellular matrix components. (2) The integrin alpha3beta1 binding on laminin-5 was localized in the G2 domain using a series of bacterially produced recombinant fragments derived from different domains of laminin-5. (3) Novel isoforms of paxillin, a crucial adaptor molecule associated with integrins and cytoskeletons, were identified. One of the isoforms, designated paxillin gamma, was found to lack the ability to bind vinculin. (4) Importance of the heparin-binding fomain of HB-EGF,a membrane-bound cell growth factor, in its association with the cell surface EGF receptors was demonstrated, being consistent with the previous findings that cell surface heparan sulfate proteoglycans were involved in the binding of HB-EGF with EGF receptors. (5) Laminin-1 and IGF-1 (insulin-like growth factor-1) were found to be key factors in the maintenance of differentiated phenotypes of smooth muscle cells. (6) Mouse L cells transfected with E-cadherin cDNA were found to be more adhesive onto the substrates, particularly those coated with collagen type IV.Overexpression of E-cadherin was also found to suppress the growth of leukemic cells.