Growth Hormone Induced Activation and Regulation of JAK2 and STAT Proteins

Kurzer, Jason H.; Carter‐Su, Christin

doi:10.1007/978-94-017-3000-6_12

Cited by 3 publications

(3 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1b). Once bound to these sites on the activated GHR-JAK2 complex, Stats 1, 3, 5a and 5b are thought to be phosphorylated by JAK2 after which they dimerize, translocate to the nucleus and act as transcription factors for many important GH-regulated genes [30,32,33]. Many past and recent studies have shown that activation of Stat5a and Stat5b is critical for a variety of GH functions, including changes in metabolism, body growth and sex-dependent liver gene regulation (reviewed in [30,33].…”

Section: Gh Regulation Of Stat Transcription Factorsmentioning

confidence: 99%

Recent advances in growth hormone signaling

Lanning

Carter‐Su

2006

Rev Endocr Metab Disord

Self Cite

205

163

View full text Add to dashboard Cite

Growth hormone (GH) is a major regulatory factor for overall body growth as evidenced by the height extremes in people with abnormal circulating GH levels or GH receptor (GHR) disruptions. GH also affects metabolism, cardiac and immune function, mental agility and aging. Currently, GH is being used therapeutically for a variety of clinical conditions including promotion of growth in short statured children, treatment of adults with GH deficiency and HIV-associated wasting. To help reveal previous unrecognized functions of GH, better understand the known functions of GH, and avoid adverse consequences that are often associated with exogenous GH administration, careful delineation of the molecular mechanisms whereby GH induces its diverse effects is needed. GH is a peptide hormone that is secreted into the circulation by the anterior pituitary and acts upon various target tissues expressing GHR. GH binding of GHR activates the tyrosine kinase Janus kinase 2 (JAK2), thus initiating a multitude of signaling cascades that result in a variety of biological responses including cellular proliferation, differentiation and migration, prevention of apoptosis, cytoskeletal reorganization and regulation of metabolic pathways. A number of signaling proteins and pathways activated by GH have been identified, including JAKs, signal transducers and activators of transcription (Stats), the mitogen activated protein kinase (MAPK) pathway, and the phosphatidylinositol 3'-kinase (PI3K) pathway. Although these signal transduction pathways have been well characterized, the manner by which GH activates these pathways, the downstream signals induced by these pathways, and the cross-talk with other pathways are not completely understood. Recent findings have added vital information to our understanding of these downstream signals induced by GH and mechanisms that terminate GH signaling, and identified new GH signaling proteins and pathways. This review will highlight some of these findings, many of which are unexpected and some of which challenge previously held beliefs about the mechanisms of GH signaling.

show abstract

Section: Gh Regulation Of Stat Transcription Factorsmentioning

confidence: 99%

Recent advances in growth hormone signaling

Lanning

Carter‐Su

2006

Rev Endocr Metab Disord

Self Cite

205

163

View full text Add to dashboard Cite

show abstract

“…The JAK-STAT pathway is considered as the main pathway by which GH affects gene transcription [ 24 ]. Stats 5a and 5b are involved in the synthesis of several GH-sensitive genes, including insulin-like growth factor 1 (IGF-1) and the acid labile subunit (ALS), a vital part of the IGF binding protein complex (IGF1-IGFBP 3-ALS) [ 25 ]. Tyrosyl phosphorylation of IRS proteins would be triggered by JAK2 activation, which promotes the recruitment of PI3K, regulating glucose transport and probably other cellular responses [ 26 ].…”

Section: Ghr Function and Structurementioning

confidence: 99%

The Exon 3-Deleted Growth Hormone Receptor (d3GHR) Polymorphism—A Favorable Backdoor Mechanism for the GHR Function

Falah,

Sharvit,

Atzmon

2023

IJMS

View full text Add to dashboard Cite

Growth hormone (GH) is a peptide hormone that plays a crucial role in controlling growth, development, and lifespan. Molecular regulation of GH is accomplished via the GH receptor (GHR), which is the main factor influencing human development and is essential to optimal functioning of the GH/IGF-I axis. Two GHR isoforms have been studied, according to the presence (flGHR) or absence (d3GHR) of exon 3. The d3GHR isoform, which lacks exon 3 has recently been related to longevity; individuals carrying this isoform have higher receptor activity, improved signal transduction, and alterations in the treatment response and efficacy compared with those carrying the wild type (WT) isoform (flGHR). Further, studies performed in patients with acromegaly, Prader–Willi syndrome, Turner syndrome, small for gestational age (SGA), and growth hormone deficiency (GHD) suggested that the d3GHR isoform may have an impact on the relationship between GH and IGF-I levels, height, weight, BMI, and other variables. Other research, however, revealed inconsistent results, which might have been caused by confounding factors, including limited sample sizes and different experimental methods. In this review, we lay out the complexity of the GHR isoforms and provide an overview of the major pharmacogenetic research conducted on this ongoing and unresolved subject.

show abstract

“…The JAK-STAT pathway is considered as the main pathway by which GH affects gene transcription [18]. Stats 5a and 5b are involved in the synthesis of several GH-sensitive genes, including insulin-like growth factor 1 (IGF-1) and the acid labile subunit (ALS), a vital part of the IGF binding protein complex (IGF1-IGFBP 3-ALS) [19]. Tyrosyl phosphorylation of IRS proteins would be triggered by JAK2 activation, which promotes the recruitment of PI3K, regulating glucose transport and probably other cellular responses [20].…”

Section: Ghr Function and Structurementioning

confidence: 99%

The Exon 3-Deleted Growth Hormone Receptor (d3GHR) Polymorphism - a Favorable Backdoor Mechanism for the GHR Function

Falah,

Sharvit,

Atzmon

2023

Preprint

View full text Add to dashboard Cite

Growth hormone (GH) is a peptide hormone that plays a crucial role in controlling growth, development, and lifespan. Molecular regulation of GH is accomplished via the GH receptor (GHR) gene, which is the main factor influencing human development and is essential to optimal functioning of the GH/IGF-I axis. Two GHR isoforms have been studied, according to the presence (flGHR) or absence (d3GHR) of exon 3. The d3GHR variant, which has recently been related to longevity, is associated with enhanced signal transduction and higher receptor function. Many of these studies indicated that the growth response to GH treatment may be affected. Individuals carrying the d3GHR isoform have higher receptor activity, improved signal transduction, and alterations in the treatment response and efficacy compared with those carrying the WT isoform. Further, studies performed in patients with acromegaly, Prader-Willi syndrome, Turner syndrome, small for gestational age (SGA), and growth hormone deficiency (GHD) suggested that the d3GHR variant may have an impact on the relationship between GH and IGF-I levels, height, weight, BMI, and other variables. Other research, however, revealed inconsistent results, which might have been caused by confounding factors, including limited sample sizes and different experimental methods. In this review, we lay out the complexity of the GHR isoforms and provide an overview of the major pharmacogenetic research conducted on this ongoing and unresolved subject.

show abstract

Growth Hormone Induced Activation and Regulation of JAK2 and STAT Proteins

Cited by 3 publications

References 91 publications

Recent advances in growth hormone signaling

Recent advances in growth hormone signaling

The Exon 3-Deleted Growth Hormone Receptor (d3GHR) Polymorphism—A Favorable Backdoor Mechanism for the GHR Function

The Exon 3-Deleted Growth Hormone Receptor (d3GHR) Polymorphism - a Favorable Backdoor Mechanism for the GHR Function

Contact Info

Product

Resources

About