This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager NURSA Molecule Pages Link Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jin, H. Articles by Carter-Su, C. Search for Related Content PubMed PubMed Citation Articles by Jin, H. Articles by Carter-Su, C.

JAK2, But Not Src Family Kinases, Is Required for STAT, ERK, and Akt Signaling in Response to Growth Hormone in Preadipocytes and Hepatoma Cells

Department of Molecular and Integrative Physiology (H.J., C.C.-S.), Graduate Program in Cellular and Molecular Biology (N.J.L., C.C.-S.), University of Michigan Medical School, Ann Arbor, Michigan 48109-5622

Address all correspondence and requests for reprints to: Dr. Christin Carter-Su, Department of Molecular and Integrative Physiology, The University of Michigan Medical School, Ann Arbor, Michigan 48109-5622. E-mail: cartersu{at}umich.edu.

Janus kinase 2 (JAK2), a tyrosine kinase that associates with the GH receptor and is activated by GH, has been implicated as a key mediator of GH signaling. Several published reports suggest that members of the Src family of tyrosine kinases may also participate in GH signaling. We therefore investigated the extent to which JAK2 and Src family kinases mediate GH activation of signal transducers and activators of transcription (STATs) 1, 3, and 5a/b, ERKs 1 and 2, and Akt, in the highly GH-responsive cell lines 3T3-F442A preadipocytes and H4IIE hepatoma cells. GH activation of Src family kinases was not detected in either cell line. Further, blocking basal activity of Src kinases with the Src inhibitors PP1 and PP2 did not inhibit GH activation of STATs 1, 3, or 5a/b, or ERKs 1 and 2. When levels of JAK2 were depressed by short hairpin RNA in 3T3-F442A and H4IIE cells, GH-stimulated activation of STATs 1, 3, and 5a/b, ERKs 1 and 2, and Akt were significantly reduced; however, basal activity of Src family kinases was unaffected. These results were supported genetically by experiments showing that GH robustly activates JAK2, STATs 3 and 5a/b, ERKs 1 and 2, and Akt in murine embryonic fibroblasts derived from Src/Yes/ Fyn triple-knockout embryos that lack known Src kinases. These results strongly suggest that JAK2, but not Src family kinases, is critical for transducing these GH signals in 3T3-F442A and H4IIE cells.

NURSA Molecule Pages Link:

Nuclear Receptors:   REV-ERBα

Coregulators:   HDAC3  |  AIB1  |  NCOR

This article has been cited by other articles:

				X. Wang, N. Yang, L. Deng, X. Li, J. Jiang, Y. Gan, and S. J. Frank Interruption of Growth Hormone Signaling via SHC and ERK in 3T3-F442A Preadipocytes upon Knockdown of Insulin Receptor Substrate-1 Mol. Endocrinol., April 1, 2009; 23(4): 486 - 496. [Abstract] [Full Text] [PDF]