RPTPmu and protein tyrosine phosphorylation regulate K(+) channel mRNA expression in adult cardiac myocytes.
Previously, we reported that cell-cell contact regulates K(+) channel mRNA expression in cultured adult rat cardiac myocytes. Here we show that exposing cardiac myocytes to tyrosine kinase inhibitors (genistein, tyrphostin A25), but not inactive analogs, prevents downregulation of Kv1.5 mRNA and upregulation of Kv4.2 mRNA normally observed when they are cultured under low-density conditions. Furthermore, cardiac myocytes cocultured with cells that endogenously (Mv 1 Lu) or heterologously (Chinese hamster ovary cells) express the receptor-type protein tyrosine phosphatase mu (RPTPmu) display Kv1.5 mRNA levels paralleling that which was observed in myocytes cultured under high-density conditions and in intact tissue. In contrast, myocytes cocultured with control cells failed to produce this response. Finally, it is shown that Kv4.2 mRNA expression is unaffected by RPTPmu. These findings reveal that multiple tyrosine phosphorylation-dependent mechanisms control cardiac myocyte K(+) channel genes. Furthermore, we conclude that RPTPmu specifically regulates cardiac myocyte Kv1.5 mRNA expression. Thus this receptor protein tyrosine phosphatase may be important in responses to pathological conditions associated with the loss of cell-cell interactions in the heart.
Hershman
K M
KM
Department of Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Levitan
E S
ES
D000367:Age Factors; D000818:Animals; D016466:CHO Cells; D002450:Cell Communication / Q000235:genetics; D006224:Cricetinae; D015536:Down-Regulation / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D019833:Genistein / Q000494:pharmacology; D006352:Heart Ventricles / Q000737:chemistry / Q000166:cytology / Q000201:enzymology; D015640:Ion Channel Gating / Q000502:physiology; D007529:Isoflavones / Q000494:pharmacology; D051666:Kv1.5 Potassium Channel; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000166:cytology / Q000201:enzymology; D009206:Myocardium / Q000737:chemistry / Q000166:cytology / Q000201:enzymology*; D010766:Phosphorylation; D015221:Potassium Channels / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D051672:Shal Potassium Channels; D015398:Signal Transduction / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism*
D004791:Enzyme Inhibitors; D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; C496983:Kcna5 protein, rat; D051666:Kv1.5 Potassium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D051672:Shal Potassium Channels; D014443:Tyrosine; C004742:daidzein; D019833:Genistein; D017027:Protein Tyrosine Phosphatases; C516864:Ptprn protein, rat; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8