The alpha 5 alpha 1 integrin, a fibronectin receptor, has been implicated in the control of cell growth and the regulation of gene expression. We report that disruption of ligation between alpha 5 alpha 1 and fibronectin by integrin alpha 5 subunit or fibronectin monoclonal antibodies stimulated DNA synthesis in growth-arrested FET @entity1 @entity694 cells. This stimulation only occurred when monoclonal antibody was added in the early G1 phase of the cell cycle after release from quiescence by fresh medium. Stimulation of DNA synthesis by alpha 5 or fibronectin antibody was concentration- and time-dependent. FET cells expressed alpha 4 beta 1 integrin (another fibronectin receptor); however, addition of anti-human @entity5690 monoclonal antibody had no effect on DNA synthesis. Treatment with alpha 5 monoclonal antibody led to a marked increase in the expression of @entity8985 in G1 phase of the cell cycle and consequently increased the phosphorylation of @entity995 protein. alpha 5 monoclonal antibody treatment increased both @entity7596 - and @entity1364 E-associated kinase activity which was accompanied by increased protein levels of @entity15308 and @entity7596 . Western blotting of immunoprecipitates demonstrated increased @entity15308 - @entity1364 E and @entity15308 - @entity7596 complexes in cells treated with alpha 5 monoclonal antibody. Furthermore, disruption of alpha 5 alpha 1/fibronectin ligation activated mitogen-activated protein kinase @entity10368 and @entity3903 ( @entity3962 ). Pretreatment of the cells with a specific inhibitor of @entity12363 , @entity4286 , blocked the alpha 5 monoclonal antibody-induced mitogen-activated protein kinase activity. In addition @entity4286 prevented alpha 5 monoclonal antibody-induced DNA synthesis. Since alpha 5 alpha 1 ligation to fibronectin is associated with @entity851 , our results indicate that ligation of alpha 5 alpha 1 integrin to fibronectin results in suppressed mitogen-activated protein kinase activity which in turn inhibits @entity1364 -dependent kinase activity in growth-arrested cells.

Disruption of fibronectin binding to the alpha 5 beta 1 integrin stimulates the expression of XXXX -dependent kinases and DNA synthesis through activation of extracellular signal-regulated kinase.

@entity1 :: ('9606', 'Species') :: ['human'] @entity1364 :: ('5111', 'Gene') :: ['cyclin'] @entity851 :: ('MESH:D006130', 'Disease') :: ['decreased growth parameters'] @entity8985 :: ('1019', 'Gene') :: ['CDK4'] @entity3962 :: ('5594;5595', 'Gene') :: ['extracellular signal-regulated kinase 1 and 2'] @entity10368 :: ('10561', 'Gene') :: ['p44'] @entity12363 :: ('5604', 'Gene') :: ['MEK-1'] @entity15308 :: ('1017', 'Gene') :: ['CDK2'] @entity7596 :: ('890', 'Gene') :: ['cyclin A'] @entity4286 :: ('MESH:C093973', 'Chemical') :: ['PD98059'] @entity5690 :: ('3676', 'Gene') :: ['integrin alpha 4'] @entity694 :: ('MESH:D003110', 'Disease') :: ['colon carcinoma'] @entity3903 :: ('23552', 'Gene') :: ['p42'] @entity995 :: ('MESH:D012175', 'Disease') :: ['retinoblastoma']
@entity1364 :: (5111,Gene) :: ['cyclin']
