Deactivation of regulatory proteins hnRNP A1 and A2 during SC-1 induced apoptosis.
Phosphorylation and activation of caspases play an important role in the induction of apoptosis. During tumor specific apoptosis, induced by the human monoclonal antibody SC-1, tyrosine phosphorylation and serine dephosphorylation of several proteins is observed. In this paper we describe the identification of two dephosphorylated proteins as heterogeneous nuclear ribonucleoproteins A1 and A2 (hnRNP A1, hnRNP A2). The dephosphorylation of these proteins is important for apoptosis since the amount of apoptotic cell death can be decreased by the specific serine/threonine phosphatase inhibitor okadaic acid. We also investigated the effect of serine kinase inhibitor H7 on SC-1 induced apoptosis, which leads to a dose dependent increase in apoptosis. We could also show that 24 hours after the induction of apoptosis the hnRNP A1 protein is cleaved into different cleavage products. Further, we found a decreased expression of caspase-2 in early apoptosis signalling and an overexpression 24 hours after induction of apoptosis. Our results show that the phosphorylation status of the hnRNP A1 and A2 plays a significant role in early SC-1 induced apoptosis signalling and further indicate the role of caspase activation during the apoptotic process.
Hermann
R
R
Institute of Pathology, Josef-Schneider-Str. 2, D-97080 Würzburg, Germany.
Hensel
F
F
Müller
E C
EC
Keppler
M
M
Souto-Carneiro
M
M
Brändlein
S
S
Müller-Hermelink
H K
HK
Vollmers
H P
HP
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology*; D061067:Antibodies, Monoclonal, Humanized; D017209:Apoptosis / Q000276:immunology*; D053143:Caspase 2; D020169:Caspases / Q000378:metabolism; D018076:DNA, Complementary; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D006868:Hydrolysis; D010766:Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012261:Ribonucleoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D013274:Stomach Neoplasms / Q000276:immunology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018076:DNA, Complementary; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D012261:Ribonucleoproteins; C111124:SC-1 monoclonal antibody; C439768:hnRNP A2; D053143:Caspase 2; D020169:Caspases