1978

Fibronectin shown to colocalize with fibrillar actin. Proposed a transmembrane relationship between microfilaments and FN

First evidence of affinity modulation of matrix receptors

1979 1984 1985

1 integrin shown to colocalize with extracellular focal adhesions and intracellular cytoskeletal components

1986

Talin shown to associate with 1. Demonstrated physical association of cytoskeletal proteinwith 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 modulationof integrins involves conformational changes

1987 1988

Integrin adhesioninduces transcriptionof 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

1991 1994

2 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

64 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

IIb3 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

Casein production in mammary epithelial cells requires proper matrix attachment

19951996

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

20001997

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