Beta 1 integrins signal lipid second messengers required during cell adhesion.
Clustering of integrin receptors during cell adhesion stimulates signal transduction across the cell membrane. Second messengers are generated, activating cytosolic proteins and causing cytoskeletal assembly and rearrangement. HeLa cell adhesion to a collagen substrate has been shown to initiate an arachidonic acid-mediated signaling pathway, leading to the activation of protein kinase C (PKC) and cell spreading. To determine the role of integrin receptors in triggering this signaling pathway, monoclonal antibodies to beta 1 integrins were used to either cluster integrins on the cell surface or to provide an integrin-dependent substrate for cell adhesion. Using this approach, we have defined a pathway required for cell spreading that can be initiated by the ligation of integrins and leads to the activation of PKC. Specifically, our results indicate that clustering beta 1 integrins results in the activation of phospholipase A2 leading to the production of arachidonic acid and the activation of PKC.
Auer
K L
KL
Department of Biochemistry and Molecular Biology, University of Massachusetts at Amherst 01003, USA.
Jacobson
B S
BS
D000098:Acetophenones / Q000494:pharmacology; D000911:Antibodies, Monoclonal; D016718:Arachidonic Acid / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005780:Gelatin; D006367:HeLa Cells; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism / Q000502:physiology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D010084:Oxidation-Reduction; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D011493:Protein Kinase C / Q000502:physiology; D015290:Second Messenger Systems / Q000502:physiology*
D000098:Acetophenones; D000911:Antibodies, Monoclonal; D004791:Enzyme Inhibitors; D019012:Integrin beta1; D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; D005780:Gelatin; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2; C006821:4-bromophenacyl bromide