Src transduces signaling via growth hormone (GH)-activated GH receptor (GHR) tyrosine-phosphorylating GHR and STAT5 in human leukemia cells.
Most human leukemia cells are shown to express growth hormone receptor (GHR) and some of them proliferate in response to GH. We demonstrate that Src contributes to GHR-mediated signal transduction via STAT5 activation in F-36P human leukemia cells stimulated with GH. The tyrosine phosphorylation levels of GHR and STAT5 induced by GH decreased in the presence of PP2 Src kinase inhibitor. When GHR and wild-type Src were co-expressed in COS7 cells, GHR was markedly tyrosine phosphorylated as well as when Jak2 was co-expressed with GHR, but not when kinase-inactive Src co-expressed. The treatment of F-36P cells with the antisense src oligonucleotides, which selectively decreased the Src expression, reduced the rhGH-induced tyrosine phosphorylation of the STAT5 activation sites.
Manabe
Noriko
N
Depertment of Laboratory Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
Kubota
Yoshitsugu
Y
Kitanaka
Akira
A
Ohnishi
Hiroaki
H
Taminato
Tomohiko
T
Tanaka
Terukazu
T
D045744:Cell Line, Tumor; D013006:Growth Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011986:Receptors, Somatotropin / Q000187:drug effects* / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000187:drug effects / Q000378:metabolism*; D019061:src-Family Kinases / Q000187:drug effects / Q000378:metabolism*
D016376:Oligonucleotides, Antisense; D047428:Protein Kinase Inhibitors; D011986:Receptors, Somatotropin; D050799:STAT5 Transcription Factor; D014443:Tyrosine; D013006:Growth Hormone; D019061:src-Family Kinases