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1978 Fibronectin shown to colocalize with fibrillar actin. Proposed a transmembrane relationship between microfilaments and FN First evidence of affinity.

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Presentation on theme: "1978 Fibronectin shown to colocalize with fibrillar actin. Proposed a transmembrane relationship between microfilaments and FN First evidence of affinity."— Presentation transcript:

1 1978 Fibronectin shown to colocalize with fibrillar actin. Proposed a transmembrane relationship between microfilaments and FN First evidence of affinity modulation of matrix receptors integrin shown to colocalize with extracellular focal adhesions and intracellular cytoskeletal components 1986 Talin shown to associate with 1. Demonstrated physical association of cytoskeletal protein with integrin First full length subunit and partial subunit cDNAs cloned Receptors for matrix proteins purified 1964 Anchorage dependence defined 1968 Addition of fibronectin to tumor cells induces cell flattening and reorganization of the actin cytoskeleton 1977 Mammary epithelial cells could be induced to produce milk proteins when cultured on floating collagen gels The shape of adherent cells found to be a critical determinant of cell proliferation RGD defined as the minimal cell binding motif of ECMs First evidence of v- Src localization to focal adhesions 1980 Phosphotyrosine is detected in focal adhesions 2 integrin deficiency in humans results in impaired immune function Evidence that affinity modulation of integrins involves conformational changes

2 Integrin adhesion induces transcription of cellular genes 1989 Integrins control induction of tyrosine phosphorylation 1993 Adhesion required for cyclinA induction by growth factors Rho, Rac and Cdc42 regulate the production of focal adhesions/stress fibers and lamellipodia PKC found to localize to FA Engagement of integrins strongly enhances TCR response integrins also undergo affinity modulation 1990 Cytoplasmic tails of integrins regulate affinity for ligand 1992 Epithelial and endothelial cells require attachment to matrix for survival 6 4 localizes to hemidesmosomes 1 integrin engagement controls the differentiation of keratinocytes Integrins and Fc receptors cooperate in induction of oxidative burst in neutrophils Attachment to matrix induces Erk activation Antibodies to 1 block differentiation of myoblasts Na-H antiporters, which regulate intracellular pH, were found to be regulated by integrins IIb 3 integrin mutations in platelets responsible for Glanzmann thrombasthenia FAK is cloned and shown to be 120kD protein that is tyrosine phosphorylated after attachment of cells to integrins

3 Casein production in mammary epithelial cells requires proper matrix attachment Cyclin D induction and p21/p27 downregulation by growth factors requires matrix attachment Prolonged activation of Erk by growth factors requires integrin adhesion 2001 Integrin activation of Rac is required for cyclin D translation and progression through G1 Integrin subunits interact with caveolin and transduce signals to Erk through Fyn and Shc EGFR and 1 exert recipricol effects on transformed cells in normal 3D organization Adhesion is sufficient for induction of lamellipodia, filopodia and focal adhesion formation 1999 Syndecans cooperative with integrins in focal adhesion formation 1998 Pathway from Cas to Crk to DOCK180 to Rac identified Integrins transactivate growth factor receptors 3D matrices induce formation of novel focal adhesion structures not detected when cells are grown on immobilized martrix Identification of a novel integrin induced pathway that regulates the Rho family GEF, Vav Adhesion to matrix activates Rho and Rac FAK knock-out demonstrates the involvement of FAK in focal adhesion turnover 1 integrin knock-out demonstrates role of integrins in mammalian development


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