Membrane and morphological changes in apoptotic cells regulated by caspase-mediated activation of PAK2.
Apoptosis of Jurkat T cells induced the caspase-mediated proteolytic cleavage of p21-activated kinase 2 (PAK2). Cleavage occurred between the amino-terminal regulatory domain and the carboxyl-terminal catalytic domain, which generated a constitutively active PAK2 fragment. Stable Jurkat cell lines that expressed a dominant-negative PAK mutant were resistant to the Fas-induced formation of apoptotic bodies, but had an enhanced externalization of phosphatidylserine at the cell surface. Thus, proteolytic activation of PAK2 represents a guanosine triphosphatase-independent mechanism of PAK regulation that allows PAK2 to regulate morphological changes that are seen in apoptotic cells.
Rudel
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Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Bokoch
G M
GM
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis; D001665:Binding Sites; D053148:Caspase 3; D020169:Caspases; D002462:Cell Membrane / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation; D053222:Fas Ligand Protein; D006801:Humans; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000201:enzymology; D054462:p21-Activated Kinases
D000590:Amino Acid Chloromethyl Ketones; D015853:Cysteine Proteinase Inhibitors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; C098738:N-acetyl-tyrosyl-valyl-alanyl-aspartyl chloromethyl ketone; D010718:Phosphatidylserines; D011994:Recombinant Proteins; C515907:PAK2 protein, human; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases