Down-regulation of proteolytic activity in 12-O-tetradecanoyl-phorbol-13-acetate-induced K562 leukemia cell cultures: depletion of active urokinase by excess type 1 plasminogen activator inhibitor

Journal of Cellular Physiology
R AlitaloR Stephens

Abstract

The human chronic myeloid leukemia cell line K562 acquires several megakaryoblastoid features when cultured in the presence of the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA). We observed strongly increased secretion of several proteins into the culture media of K562 cells within a few hours of TPA treatment. Two of the major secreted polypeptides were identified by immunoprecipitation from media of metabolically labeled cultures as the tissue inhibitor of metalloproteinases (TIMP) and the type 1 plasminogen activator inhibitor (PAI-1). Maximal amounts of PAI-1 mRNA and secretion of PAI-1 polypeptides were observed after 24 hr of TPA treatment and PAI-1 persisted at elevated levels for several days. The induction of PAI-1 mRNA was dependent on de novo protein synthesis. Uninduced and induced cells secreted urokinase plasminogen activator in its single-chain proenzyme form (pro-u-PA), which was cleaved extracellularly to the active two-chain form as shown by pulse-chase labeling experiments. Upon TPA induction, the secretion of u-PA polypeptides increased severalfold, and there was a transient accumulation of pro-u-PA in the culture medium. However, this did not lead to increased u-PA activity in the cultures, sin...Continue Reading

References

May 15, 1976·International Journal of Cancer. Journal International Du Cancer·C Sundström, K Nilsson
Nov 12, 1985·Biochimica Et Biophysica Acta·O Saksela
Jan 1, 1985·Advances in Cancer Research·K DanøL Skriver
Apr 1, 1987·The Journal of Cell Biology·F BlasiK Danø
Sep 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·T NyD J Loskutoff
Dec 24, 1987·Journal of Immunological Methods·R StephensA Vaheri
Nov 4, 1988·Cell·T Curran, B R Franza
Jan 1, 1988·Annual Review of Cell Biology·O Saksela, D B Rifkin
May 1, 1986·Molecular and Cellular Biology·O R ColamoniciL M Neckers
Jul 1, 1985·Journal of Clinical Pathology·N A BoothB Bennett
Dec 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·L A EricksonD J Loskutoff
Jan 1, 1984·Leukemia Research·P A TetterooA E von dem Borne
Apr 1, 1981·The Biochemical Journal·T E CawstonJ J Reynolds
Oct 1, 1984·The Journal of Clinical Investigation·L A EricksonD J Loskutoff
Mar 12, 1984·FEBS Letters·P KristensenK Danø
Jan 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·T EdlundS Josephson
Aug 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·P VerdeF Blasi

❮ Previous
Next ❯

Citations

Dec 2, 1990·Cell Differentiation and Development : the Official Journal of the International Society of Developmental Biologists·A VaheriH Tapiovaara
Sep 10, 1994·Annals of the New York Academy of Sciences·A VaheriJ Bizik
Feb 1, 1993·International Journal of Cancer. Journal International Du Cancer·H TapiovaaraA Vaheri
Feb 1, 1992·International Journal of Cancer. Journal International Du Cancer·K SumiyoshiS Baba

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.