1978

1. Fibronectin shown to colocalize with fibrillar actin. Proposed a transmembrane relationship between microfilaments and FN Phosphotyrosine is detected in focal adhesions Receptors for matrix proteins purified Addition of fibronectin to tumor cells induces cell flattening and reorganization of the actin cytoskeleton First full length b subunit and partial a subunit cDNAs cloned First evidence of v-Src localization to focal adhesions RGD defined as the minimal cell binding motif of ECMs Anchorage dependence defined 1964 1968 1977 1979 1984 1985 1986 1978 1980 The shape of adherent cells found to be a critical determinant of cell proliferation Mammary epithelial cells could be induced to produce milk proteins when cultured on floating collagen gels First evidence of affinity modulation of matrix receptors Evidence that affinity modulation of integrins involves conformational changes b1 integrin shown to colocalize with extracellular focal adhesions and intracellular cytoskeletal components Talin shown to associate with b1. Demonstrated physical association of cytoskeletal protein with integrin b2 integrin deficiency in humans results in impaired immune function

2. aIIbb3 integrin mutations in platelets responsible for Glanzmann thrombasthenia Integrins and Fc receptors cooperate in induction of oxidative burst in neutrophils a6b4 localizes to hemidesmosomes FAK is cloned and shown to be 120kD protein that is tyrosine phosphorylated after attachment of cells to integrins Epithelial and endothelial cells require attachment to matrix for survival Attachment to matrix induces Erk activation Antibodies to b1 block differentiation of myoblasts Integrins control induction of tyrosine phosphorylation 1987 1988 1992 1993 1989 1990 1991 1994 Rho, Rac and Cdc42 regulate the production of focal adhesions/stress fibers and lamellipodia Integrin adhesion induces transcription of cellular genes Na-H antiporters, which regulate intracellular pH, were found to be regulated by integrins Adhesion required for cyclinA induction by growth factors Cytoplasmic tails of integrins regulate affinity for ligand b2 integrins also undergo affinity modulation b1 integrin engagement controls the differentiation of keratinocytes Engagement of integrins strongly enhances TCR response PKC found to localize to FA

3. Casein production in mammary epithelial cells requires proper matrix attachment Integrin a subunits interact with caveolin and transduce signals to Erk through Fyn and Shc Pathway from Cas to Crk to DOCK180 to Rac identified Integrin activation of Rac is required for cyclin D translation and progression through G1 b1 integrin knock-out demonstrates role of integrins in mammalian development EGFR and b1 exert recipricol effects on transformed cells in normal 3D organization Identification of a novel integrin induced pathway that regulates the Rho family GEF, Vav 1995 1997 1998 1996 1999 2000 2001 FAK knock-out demonstrates the involvement of FAK in focal adhesion turnover Adhesion to matrix activates Rho and Rac Adhesion is sufficient for induction of lamellipodia, filopodia and focal adhesion formation Prolonged activation of Erk by growth factors requires integrin adhesion Integrins transactivate growth factor receptors Syndecans cooperative with integrins in focal adhesion formation 3D matrices induce formation of novel focal adhesion structures not detected when cells are grown on immobilized martrix Cyclin D induction and p21/p27 downregulation by growth factors requires matrix attachment