A requirement for K+-channel activity in growth factor-mediated extracellular signal-regulated kinase activation in human myeloblastic leukemia ML-1 cells

Blood. 1999 Jul 1;94(1):139-45.


Voltage-gated K+ channels have been shown to be required for proliferation of various types of cells. Much evidence indicates that K+-channel activity is required for G1 progression of the cell cycle in different cell backgrounds, suggesting that K+-channel activity is required for early-stage cell proliferation in these cells. However, little is known about the molecular mechanisms that underlie this phenomenon. We have shown in human myeloblastic leukemia ML-1 cells that K+ channels are activated by epidermal growth factor (EGF), whereas serum starvation deprivation suppressed their activity. In addition, voltage-gated K+ channels are required for G1/S-phase transition of the cell cycle. We report here that suppression of K+ channels prevented the activation of extracellular signal-regulated protein kinase 2 (ERK-2) in response to EGF and serum. However, blockade of K+ channels did not prevent ERK-2 activation induced by 12-O-tetradecanoyl-phorbol 13-acetate (TPA). Elimination of extracellular Ca2+ did not alter either ERK-2 activation or the effect of K+-channel blockade on ERK-2 activation. Our data demonstrate that the K+ channel is a part of the EGF-mediated mitogenic signal-transduction process and is required for initiation of the EGF-mediated mitogen-activated protein kinase (MAPK) pathways. Our findings may thus explain why an increase in K+-channel activity is associated with cell proliferation in many types of cells, including ML-1 cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Calcium-Calmodulin-Dependent Protein Kinases / physiology*
  • Carcinogens / pharmacology
  • Enzyme Activation / drug effects
  • Epidermal Growth Factor / pharmacology*
  • G1 Phase / physiology
  • Humans
  • Leukemia, Myeloid, Acute / pathology
  • Leukemia, Myeloid, Acute / physiopathology*
  • Mitogen-Activated Protein Kinase 1
  • Potassium Channels / physiology*
  • Signal Transduction / drug effects
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Cells, Cultured


  • Carcinogens
  • Potassium Channels
  • Epidermal Growth Factor
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Tetradecanoylphorbol Acetate