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Protein kinase inhibitors exert stage specific and inducer dependent effects on HL-60 cell differentiation.
Anticancer Res. 1995 May-Jun; 15(3):687-92.AR

Abstract

The human promyelocytic leukemia cell line HL-60 was induced to differentiate to mature granulocytic cells by dbcAMP or RA. The influence of distinct protein kinases during different stages of this differentiation was studied by the use of H8, staurosporine and genistein as inhibitors of PKA, PKC and PTK respectively. In dbcAMP-mediated differentiation, the PKA activity of uninduced cells is crucial for the induction of differentiation, but therefore its significance drastically declines and a more important role is played by PKC and PTK. In RA-mediated differentiation, the native state of PKA and PKC activities are necessary and of similar importance for induction. However, the differentiation is enhanced when, following induction, the activities of PKA and PTK are normal and the activity of PKC, in contrast, is temporary suppressed. At the phenotypic stage the effect of inhibition of protein kinases on maturation is in the order PTK > PKC > PKA for the dbcAMP-mediated differentiation and PKC > PKA > PTK for the RA-mediated differentiation. The results indicate that protein kinase activities during differentiation are stage specific and this specificity depends on the inducer used.

Authors+Show Affiliations

Laboratory of Developmental Biology, Institute of Biochemistry, Vilnius, Lithuania.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7645944

Citation

Savickiene, J, et al. "Protein Kinase Inhibitors Exert Stage Specific and Inducer Dependent Effects On HL-60 Cell Differentiation." Anticancer Research, vol. 15, no. 3, 1995, pp. 687-92.
Savickiene J, Gineitis A, Shanbhag VP, et al. Protein kinase inhibitors exert stage specific and inducer dependent effects on HL-60 cell differentiation. Anticancer Res. 1995;15(3):687-92.
Savickiene, J., Gineitis, A., Shanbhag, V. P., & Stigbrand, T. (1995). Protein kinase inhibitors exert stage specific and inducer dependent effects on HL-60 cell differentiation. Anticancer Research, 15(3), 687-92.
Savickiene J, et al. Protein Kinase Inhibitors Exert Stage Specific and Inducer Dependent Effects On HL-60 Cell Differentiation. Anticancer Res. 1995 May-Jun;15(3):687-92. PubMed PMID: 7645944.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protein kinase inhibitors exert stage specific and inducer dependent effects on HL-60 cell differentiation. AU - Savickiene,J, AU - Gineitis,A, AU - Shanbhag,V P, AU - Stigbrand,T, PY - 1995/5/1/pubmed PY - 1995/5/1/medline PY - 1995/5/1/entrez SP - 687 EP - 92 JF - Anticancer research JO - Anticancer Res VL - 15 IS - 3 N2 - The human promyelocytic leukemia cell line HL-60 was induced to differentiate to mature granulocytic cells by dbcAMP or RA. The influence of distinct protein kinases during different stages of this differentiation was studied by the use of H8, staurosporine and genistein as inhibitors of PKA, PKC and PTK respectively. In dbcAMP-mediated differentiation, the PKA activity of uninduced cells is crucial for the induction of differentiation, but therefore its significance drastically declines and a more important role is played by PKC and PTK. In RA-mediated differentiation, the native state of PKA and PKC activities are necessary and of similar importance for induction. However, the differentiation is enhanced when, following induction, the activities of PKA and PTK are normal and the activity of PKC, in contrast, is temporary suppressed. At the phenotypic stage the effect of inhibition of protein kinases on maturation is in the order PTK > PKC > PKA for the dbcAMP-mediated differentiation and PKC > PKA > PTK for the RA-mediated differentiation. The results indicate that protein kinase activities during differentiation are stage specific and this specificity depends on the inducer used. SN - 0250-7005 UR - https://www.unboundmedicine.com/medline/citation/7645944/Protein_kinase_inhibitors_exert_stage_specific_and_inducer_dependent_effects_on_HL_60_cell_differentiation_ DB - PRIME DP - Unbound Medicine ER -