Cleavage of focal adhesion kinase by caspases during apoptosis.
Apoptotic cells undergo characteristic morphological changes that include detachment of cell attachment from the substratum and loss of cell-cell interactions. Attachment of cells to the extracellular matrix and to other cells is mediated by integrins. The interactions of integrins with the extracellular matrix activates focal adhesion kinase (FAK) and suppresses apoptosis in diverse cell types. Members of the tumor necrosis family such as Fas and Apo-2L, also known as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), induce apoptosis in both suspension and adherent cells through the activation of caspases. These caspases, when activated, cleave substrates that are important for the maintenance of nuclear and membrane integrity. In this study, we show that FAK is sequentially cleaved into two different fragments early in Apo-2L-induced apoptosis. We also demonstrate that FAK cleavage is mediated by caspases and that FAK shows unique sensitivity to different caspases. Our results suggest that disruption of FAK may contribute to the morphological changes observed in apoptotic suspension and adherent cells.
Wen
L P
LP
Department of Pulmonary and Critical Care Medicine, Stanford University, Stanford, California 94305, USA.
Fahrni
J A
JA
Troie
S
S
Guan
J L
JL
Orth
K
K
Rosen
G D
GD
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D020170:Caspase 1; D053148:Caspase 3; D053178:Caspase 6; D053179:Caspase 7; D020169:Caspases; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D015815:Cell Adhesion Molecules; D015853:Cysteine Proteinase Inhibitors; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C505407:CASP3 protein, human; C505514:CASP6 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053178:Caspase 6; D053179:Caspase 7; D020169:Caspases; D003546:Cysteine Endopeptidases; D020170:Caspase 1