PathBank

Pathway Description

Growth Hormone Signaling Pathway

Bos taurus

Category:

Protein Pathway

Sub-Categories:

Growth Factor

Kinase Signaling

Gene Regulatory

Protein/Peptide Hormone-Mediated

Cellular Response

Created: 2018-09-20

Last Updated: 2019-08-16

Growth hormone is the hormone primarily responsible for body growth. Growth hormone (GH) binds membrane-bound growth hormone receptor (GHR) to activate and enhance the binding of JAK2. This stimulates phosphorylation of JAK2 and GHR. JAK2 initiates GH signal transduction. This activation initiates multiple signalling pathways: STAT transcription factors, activation of kinases, and insulin receptor pathways. GH stimulates Signal Transducer and Activator of Transcription (STAT) and its binding to Sis-inducible elements of the c-fos promoter. C-fos expression has input from multiple pathways. The serum response element binds serum response factors and other complex transcription factors regulated by GH via the MEK/ERK pathway. STAT 5 is also involved in the synthesis of many GH-sensitive genes. STAT proteins are phosphorylated and then released from the GH/JAK2 complex. Once released, they become dimers and move to the nucleus to bind binding sites in GH-regulated genes. STAT proteins may also dimerize with other transcription factors to regulate transcription. GH can stimulate glucose transport in the cell through JAK2 stimulation of IRS proteins that recruit PI3K to regulate glucose transport.

References

Growth Hormone Signaling Pathway References

Seyfert HM, Pitra C, Meyer L, Brunner RM, Wheeler TT, Molenaar A, McCracken JY, Herrmann J, Thiesen HJ, Schwerin M: Molecular characterization of STAT5A- and STAT5B-encoding genes reveals extended intragenic sequence homogeneity in cattle and mouse and different degrees of divergent evolution of various domains. J Mol Evol. 2000 Jun;50(6):550-61.

Pubmed: 10835485

McCracken JY, Molenaar AJ, Snell RJ, Davey HW, Wilkins RJ: A polymorphic TG repeat present within the bovine STAT5A gene. Anim Genet. 1997 Dec;28(6):459.

Pubmed: 9589597

Antoniou E, Hirst BJ, Grosz M, Skidmore CJ: A single strand conformational polymorphism in the bovine gene STAT5A. Anim Genet. 1999 Jun;30(3):232.

Pubmed: 10442998

Meyer L, Brockmann G, Schwerin M, Seyfert HM: A highly polymorphic GT-repeat in the bovine STAT5B encoding gene on BTA19. Anim Genet. 1999 Feb;30(1):72.

Pubmed: 10050298

Stahl ML, Ferenz CR, Kelleher KL, Kriz RW, Knopf JL: Sequence similarity of phospholipase C with the non-catalytic region of src. Nature. 1988 Mar 17;332(6161):269-72. doi: 10.1038/332269a0.

Pubmed: 2831461

Kim JW, Sim SS, Kim UH, Nishibe S, Wahl MI, Carpenter G, Rhee SG: Tyrosine residues in bovine phospholipase C-gamma phosphorylated by the epidermal growth factor receptor in vitro. J Biol Chem. 1990 Mar 5;265(7):3940-3.

Pubmed: 1689310

Wahl MI, Nishibe S, Kim JW, Kim H, Rhee SG, Carpenter G: Identification of two epidermal growth factor-sensitive tyrosine phosphorylation sites of phospholipase C-gamma in intact HSC-1 cells. J Biol Chem. 1990 Mar 5;265(7):3944-8.

Pubmed: 1689311

Parker PJ, Coussens L, Totty N, Rhee L, Young S, Chen E, Stabel S, Waterfield MD, Ullrich A: The complete primary structure of protein kinase C--the major phorbol ester receptor. Science. 1986 Aug 22;233(4766):853-9. doi: 10.1126/science.3755547.

Pubmed: 3755547

Nishizuka Y: The molecular heterogeneity of protein kinase C and its implications for cellular regulation. Nature. 1988 Aug 25;334(6184):661-5. doi: 10.1038/334661a0.

Pubmed: 3045562

Cazaubon SM, Parker PJ: Identification of the phosphorylated region responsible for the permissive activation of protein kinase C. J Biol Chem. 1993 Aug 15;268(23):17559-63.

Pubmed: 8349635

Miller WL, Martial JA, Baxter JD: Molecular cloning of DNA complementary to bovine growth hormone mRNA. J Biol Chem. 1980 Aug 25;255(16):7521-4.

Pubmed: 6893197

Woychik RP, Camper SA, Lyons RH, Horowitz S, Goodwin EC, Rottman FM: Cloning and nucleotide sequencing of the bovine growth hormone gene. Nucleic Acids Res. 1982 Nov 25;10(22):7197-210. doi: 10.1093/nar/10.22.7197.

Pubmed: 6296767

Seeburg PH, Sias S, Adelman J, de Boer HA, Hayflick J, Jhurani P, Goeddel DV, Heyneker HL: Efficient bacterial expression of bovine and porcine growth hormones. DNA. 1983;2(1):37-45.

Pubmed: 6303731

Ge W, Davis ME, Hines HC, Irvin KM: Polymorphism in exon 10 of the bovine GHR gene detected by PCR-DGGE. Anim Genet. 1999 Apr;30(2):167-8.

Pubmed: 10376317

Hauser SD, McGrath MF, Collier RJ, Krivi GG: Cloning and in vivo expression of bovine growth hormone receptor mRNA. Mol Cell Endocrinol. 1990 Sep 10;72(3):187-200. doi: 10.1016/0303-7207(90)90143-v.

Pubmed: 2289631

Lucy MC, Boyd CK, Koenigsfeld AT, Okamura CS: Expression of somatotropin receptor messenger ribonucleic acid in bovine tissues. J Dairy Sci. 1998 Jul;81(7):1889-95. doi: 10.3168/jds.S0022-0302(98)75760-1.

Pubmed: 9710756

This pathway was propagated using PathWhiz - Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.

Propagated from SMP0063807

Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.

Visualize Compound Data

		Calcium
		D-Glucose
		Phosphate
		Water

Visualize Protein Data

		1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1
		Activated CDC42 kinase 1
		Dual specificity mitogen-activated protein kinase kinase 6
		GRB2-related adapter protein
		Growth hormone receptor
		HNF1 homeobox A
		Insulin
		Insulin receptor substrate 1
		Insulin-like growth factor 1 receptor
		Mitogen-activated protein kinase 1
		ORAI calcium release-activated calcium modulator 1
		Protein kinase C alpha type
		RAF proto-oncogene serine/threonine-protein kinase
		Rap guanine nucleotide exchange factor 2
		Ras-related protein Rap-1b
		Receptor-type tyrosine-protein phosphatase F
		Ribosomal protein S6 kinase beta-1
		Serum response factor
		SHC-transforming protein 1
		Signal transducer and activator of transcription 5A
		Signal transducer and activator of transcription 5B
		Solute carrier family 2, facilitated glucose transporter member 4
		Somatotropin
		Suppressor of cytokine signaling 2

Loading Pathway...

Growth Hormone Signaling Pathway

Growth Hormone Signaling Pathway References