PHOSPHOLIPID-SENSITIVE CA-2+-DEPENDENT PROTEIN-PHOSPHORYLATION SYSTEM IN VARIOUS TYPES OF LEUKEMIC-CELLS FROM HUMAN PATIENTS AND IN HUMAN-LEUKEMIC CELL LINE-HL60 AND LINE-K562, AND ITS INHIBITION BY ALKYL-LYSOPHOSPHOLIPID

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  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (6) , 2955-2961
Abstract
Phospholipid-sensitive Ca2+-dependent protein kinase (PL-Ca-PK), its endogenous substrate proteins, and regulation of the enzyme system by an antitumor agent alkyl-lysophospholipid (1-octadecyl-2-methyl-SD-glycero-3-phosphocholine) were investigated in various types of leukemic cells (chronic myelocytic, acute myelocytic, and acute monocytic) from patients and in 2 cultured human leukemic cell lines (HL60 and K562). Exceedingly high levels of PL-Ca-PK, largely localized in the particulate fraction, were found in all types and lines of leukemic cells; much lower levels of cAMP-dependent protein kinase and cGMP-dependent protein kinase were also found. Although numerous and similar endogenous substrates for PL-Ca-PK were found in all cell types and lines examined, substrates specific for certain leukemic cells appeared to be present. Substrate proteins for calmodulin-sensitive Ca2+-dependent protein kinase, cAMP-dependent protein kinase, and cGMP-dependent protein kinase, in comparison, were much fewer or undetected. The PL-Ca-PK activity and the phosphatidylserine-Ca2+-stimulated phosphorylation of endogenous proteins from leukemic cells were inhibited by alkyl-lysophospholipid, which acted as a competitive inhibitor of the phospholipid cofactor of the enzyme. The PL-Ca-PK system is apparently a predominant protein phosphorylation system in leukemic cells. This enzyme system may represent a site of cytotoxic action of alkyl-lysophospholipid.