Growth factor-mediated K+ channel activity associated with human myeloblastic ML-1 cell proliferation.
ML-1 cell proliferation is dependent on the presence of serum growth factors. Removing serum from the culture medium results in growth arrest and promotes differentiation. In this study, we found that a 4-aminopyridine-sensitive K+ channel was highly expressed in proliferating ML-1 cells and significantly diminished in G1-arrested ML-1 cells induced by serum deprivation but was restored within 30 min in these cells with addition of 10% fetal bovine serum (FBS) or 5 ng/ml epidermal growth factor (EGF). Intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels, but not guanosine 3',5'-cyclic monophosphate, were significantly increased in serum-deprived cells stimulated by FBS or EGF, and the effects of FBS and EGF on the channel activation were mimicked by exogenous cAMP. In inside-out patches, K+ channel activity was significantly increased by the cAMP-dependent protein kinase catalytic subunit, whereas the effect of EGF on K+ channel activation was blocked by Rp-8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphothioate. Together, our results demonstrate that serum growth factors stimulate K+ channel activity in proliferation of ML-1 cells through protein kinase-induced phosphorylation and suggest an important molecular mechanism for serum growth factor-stimulated mitogenesis in ML-1 cells.
Wang
L
L
Department of Physiology and Biophysics, School of Medicine, Wright State University, Dayton, Ohio 45435, USA.
Xu
B
B
White
R E
RE
Lu
L
L
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D017609:Barium Compounds / Q000494:pharmacology; D001769:Blood; D002417:Cattle; D002453:Cell Cycle; D002455:Cell Division; D002712:Chlorides / Q000494:pharmacology; D016895:Culture Media, Serum-Free; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D016193:G1 Phase; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D015470:Leukemia, Myeloid, Acute; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011803:Quinine / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D017609:Barium Compounds; D002712:Chlorides; D016895:Culture Media, Serum-Free; D006133:Growth Substances; D015221:Potassium Channels; D013873:Thionucleotides; C024986:barium chloride; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D004815:Epidermal Growth Factor; D019789:Tetraethylammonium; D011803:Quinine; D015761:4-Aminopyridine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D006152:Cyclic GMP; D011188:Potassium