Id |
Subject |
Object |
Predicate |
Lexical cue |
T1 |
0-87 |
Sentence |
denotes |
Cleavage and activation of p21-activated protein kinase gamma-PAK by CPP32 (caspase 3). |
T2 |
88-131 |
Sentence |
denotes |
Effects of autophosphorylation on activity. |
T3 |
132-283 |
Sentence |
denotes |
p21-activated protein kinase gamma-PAK (Pak2, PAK I) is cleaved by CPP32 (caspase 3) during apoptosis and plays a key role in regulation of cell death. |
T4 |
284-500 |
Sentence |
denotes |
In vitro, CPP32 cleaves recombinant gamma-PAK into two peptides; 1-212 contains the majority of the regulatory domain whereas 213-524 contains 34 amino acids of the regulatory domain plus the entire catalytic domain. |
T5 |
501-581 |
Sentence |
denotes |
Following cleavage, both peptides become autophosphorylated with [gamma-32P]ATP. |
T6 |
582-848 |
Sentence |
denotes |
Peptide 1-212 migrates at 27,000 daltons (p27) upon SDS-polyacrylamide gel electrophoresis and at 32,000 daltons following autophosphorylation on serine (p27P); the catalytic subunit migrates at 34,000 daltons (p34) before and after autophosphorylation on threonine. |
T7 |
849-982 |
Sentence |
denotes |
Following caspase cleavage, a significant lag (approximately 5 min) is observed before autophosphorylation and activity are detected. |
T8 |
983-1138 |
Sentence |
denotes |
When gamma-PAK is autophosphorylated with ATP(Mg) alone and then cleaved, only p27 contains phosphate, and the enzyme is inactive with exogenous substrate. |
T9 |
1139-1307 |
Sentence |
denotes |
After autophosphorylation of gamma-PAK in the presence of Cdc42(GTPgammaS) or histone 4, both cleavage products contain phosphate and gamma-PAK is catalytically active. |
T10 |
1308-1436 |
Sentence |
denotes |
Mutation of the conserved Thr-402 to alanine greatly reduces autophosphorylation and protein kinase activity following cleavage. |
T11 |
1437-1658 |
Sentence |
denotes |
Thus activation of gamma-PAK via cleavage by CPP32 is a two-step mechanism wherein autophosphorylation of the regulatory domain is a priming step, and activation coincides with autophosphorylation of the catalytic domain. |