Epidermal growth factor receptor participates in growth hormone signaling pathway in cardiac myocytes of neonatal rat.
OBJECTIVE
To examine whether growth hormone (GH) promotes the phosphorylation of epidermal growth factor (EGF) receptor and to elucidate the mechanisms by which EGF receptors were transactivated by GH stimulation.


METHODS
Cultured cardiac myocytes were stimulated by GH directly or pretreated with inhibitors before GH stimulation. The phosphorylations of EGF receptor and JAK2 were examined with immunoprecipitation followed by Western blotting using anti-phosphotyrosine antibody (4G10). The activities of extracellular signal-regulated kinases (ERKs) were assayed with the method of MBP-containing gel.


RESULTS
GH stimulated phosphorylation of EGF receptor in a time-dependent manner. Tyrphostin AG1478, a selective inhibitor of EGF receptor, strongly suppressed GH-induced ERK activation, while tyrphostin AG1295, a selective inhibitor of PDGF receptor, had no effects on the activation of ERKs stimulated by GH in cardiac myocytes. In addition, GH induced tyrosine phosphorylation of JAK2, a cytoplasmic protein tyrosine kinase, in cardiac myocytes. Moreover, tyrphostin B42, an inhibitor of JAK2 suppressed GH-induced phosphorylation of EGF receptor as well as GH-induced activation of ERKs in cardiac myocytes.


CONCLUSIONS
GH evokes the phosphorylation of EGF receptor in cardiac myocytes through activating JAK2. Phosphorylated EGF receptor plays a critical role in GH signaling pathway leading to ERK activation in cardiac myocytes.
Yuan
G
G
Department of Pathophysiology, Nantong Medical College, Qixiou Road 19, Nantong 226001, China.
Gu
Y
Y
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000378:metabolism*; D013006:Growth Hormone / Q000494:pharmacology*; D053614:Janus Kinase 2; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009206:Myocardium / Q000166:cytology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
D011518:Proto-Oncogene Proteins; D013006:Growth Hormone; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; C507927:Jak2 protein, rat; D053614:Janus Kinase 2; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases