Most signalling diagrams are long: a receptor is nudged, an adaptor arrives, a kinase phosphorylates a second kinase, that one phosphorylates a third, and several arrows later something happens to a gene. The JAK-STAT pathway is the exception. A cytokine binds outside the cell, two kinases wake each other up, and a transcription factor docks, pairs off and walks into the nucleus. That compression is the point of it, and it is why the pathway turns up wherever immune signalling or growth hormone is discussed.
This guide explains what the JAK-STAT pathway is, how a signal reaches DNA, how the pathway shuts itself off, and what human genetics shows when a piece is missing. It also settles a confusion specific to this catalogue: the growth-hormone peptides researchers ask about most do not act on this pathway at all.
The short answer
- It is the shortest route from a receptor to a gene. Ligand binding brings receptor chains together, the attached Janus kinases cross-phosphorylate, STATs dock on the phosphorylated tails, are phosphorylated themselves, pair up and enter the nucleus.
- Four kinases, seven transcription factors. Specificity comes from which JAK a receptor binds and which STAT it recruits, not from private machinery per receptor.
- STATs are activated at one tyrosine near the C-terminal end, and phosphorylation there is what lets them dimerise, bind DNA and enter the nucleus.
- The growth hormone receptor is a cytokine receptor, and JAK2 is the only JAK that binds it. The GH to JAK2 to STAT5 chain is the part growth-hormone research actually measures.
- The pathway brakes itself. STATs switch on the SOCS genes whose products then inhibit the JAKs.
- Human genetics shows how little redundancy there is. Losing JAK3 or the shared gamma chain causes severe combined immunodeficiency; dominant-negative STAT5B mutations cause growth hormone insensitivity, not deficiency.
- Sermorelin, CJC-1295 and ipamorelin do not act here. They act on G protein-coupled receptors in the pituitary, and we could find no published study measuring JAK2, STAT5 or SOCS after administering any of them.
The JAK-STAT pathway
Janus kinase · signal transducer and activator of transcription
- What it is
- A receptor-to-nucleus signalling route used by cytokine and some hormone receptors — not a peptide and not something sold
- The kinases
- JAK1 (1p31.3), JAK2 (9p24.1), JAK3 (19p13.11), TYK2 (19p13.2). TYK2’s approved name is “tyrosine kinase 2”, not “Janus kinase 4”
- The transcription factors
- Seven genes: STAT1–STAT4, STAT5A, STAT5B, STAT6. STAT5A and STAT5B are separate genes, both at 17q21.2
- Activating step
- One tyrosine near each STAT’s C-terminus: Tyr-701 on STAT1, Tyr-705 on STAT3, Tyr-694 on STAT5A, Tyr-699 on STAT5B
- DNA elements
- GAS sequences for the gamma-interferon activation factor; ISRE sequences for the ISGF3 complex of STAT1, STAT2 and IRF9
- Negative feedback
- Eight SOCS members (SOCS1–7 and CIS), the phosphatases SHP-1, SHP-2 and PTP1B, and PIAS1–4
- Named in
- A 1994 Science article by Darnell, Kerr and Stark
Where the evidence stands
- Cell and biochemical studies
- Animal genetics
- Human genetics
- Approved medicines acting on the pathway
Unusually for a pathway page, every rung is lit. What is not established is any link between this pathway and the research peptides discussed below.
What the JAK-STAT pathway is
The JAK-STAT pathway lets a signal arriving outside a cell change which genes that cell transcribes, without a long relay in between. The Janus kinases sit on the inner face of the membrane, tethered to the tails of cytokine receptors. The STAT proteins — signal transducers and activators of transcription, a name that states both jobs in order — are the transcription factors those kinases activate.
The economy of the design is the interesting part: a STAT is both the messenger and the transcription factor, so the molecule that receives the signal at the membrane is the one that binds DNA. Compare the three-tier Ras-RAF-MEK-ERK cascade, where the kinase reaching the nucleus is three enzymes removed from the receptor, or cyclic AMP and protein kinase A, where a diffusible second messenger sits in the middle. JAK-STAT has neither. It was set out under this name in a 1994 Science article by James E. Darnell Jr, Ian M. Kerr and George R. Stark; Darnell alone later received the 2002 Albert Lasker Special Achievement Award in Medical Science, which is worth stating precisely, because a shared Lasker for the three authors is not what the record shows.
How the signal crosses the membrane
Nothing physically passes through the membrane. What changes is geometry. Ligand binding causes the receptor chains to come into close proximity, which brings the JAKs on their cytoplasmic tails close enough to act on each other. The JAKs cross-phosphorylate and activate each other — the step at which an inert receptor becomes an active enzyme platform, and the step JAK inhibitors are built to block — then phosphorylate tyrosines on the receptor chains themselves, turning the tails into docking addresses.
STAT phosphorylation is thought to require SH2 domain-mediated docking to those modified chains; the hedge is the field’s own and worth keeping. An SH2 domain reads phosphotyrosine, which is why a modified tail is legible and an unmodified one is not. What follows is phosphorylation of the STATs at a single tyrosine near the C-terminal end — one phosphate, one residue. Then they pair up and go in, and the two events are coupled: for STAT5A, tyrosine phosphorylation is required for DNA-binding activity and dimerization, and STAT3 is translocated into the nucleus upon tyrosine phosphorylation and dimerization. That coupling is the mechanistic reason a single phosphate works as a switch. Inside the nucleus the targets are defined sequences: the gamma-interferon activation factor binds its cognate GAS element, while the ISGF3 complex of STAT1, STAT2 and IRF9 binds interferon-stimulated response elements instead. STAT2 shows that a STAT is not automatically a competent DNA-binding protein alone — STAT2 homodimers bind DNA very poorly, and it is the complex with IRF9 that binds the ISRE sequence.
Two cautions about the residue numbers, because they are exactly the detail that gets copied inaccurately. STAT5A’s Tyr-694 and STAT5B’s Tyr-699 are different positions in different proteins from different genes, so a bare “STAT5 Y694” covering both is wrong. And while the curated annotations attribute STAT1’s Tyr-701 phosphorylation to JAK1, JAK2 or TYK2, they do not attribute STAT3’s Tyr-705 or STAT5B’s Tyr-699 to a JAK; other kinases are listed for those sites. The residue numbers are database-solid, the kinase attribution for those sites is not, and taking residue and kinase from the same sentence is how an error enters.
Four kinases and seven STATs
There are four known JAKs in humans and seven protein-coding STAT genes.
| Protein | Location | Note worth getting right |
|---|---|---|
| JAK1 | 1p31.3 | Pairs with JAK2 at the interferon-gamma receptor and with TYK2 at type I and III interferon receptors |
| JAK2 | 9p24.1 | The only JAK that binds the growth hormone receptor; carries the V617F variant of myeloproliferative neoplasms |
| JAK3 | 19p13.11 | Constitutively associates with the interleukin receptors’ shared gamma chain; loss of function causes SCID |
| TYK2 | 19p13.2 | Approved name is “tyrosine kinase 2” — Janus is not in it. Associated with IFNAR, IL-12Rβ1, IL-10R2, gp130, IL-13Rα1 |
| STAT1, STAT2 | 750 residues (STAT1) | STAT1 is activated at Tyr-701, attributed to JAK1, JAK2 or TYK2; both partner IRF9 in the ISGF3 complex |
| STAT3 | 770 residues | Tyr-705 canonically, 704 in the Del-701 isoform. Curated isoform names are 1, Del-701 and 3 — “STAT3α/β” is literature convention only |
| STAT5A, STAT5B | 794 and 787 residues, both 17q21.2 | Tyr-694 and Tyr-699 respectively. Separate genes. “STAT5” was STAT5A’s former official symbol, which is why older papers say STAT5 and some reviews count six |
JAK2 illustrates an oddity in the architecture. Its 1132 residues include two protein kinase domains, one spanning residues 545 to 809 and a second spanning 849 to 1124, of which the second probably contains the catalytic domain — an inference-by-similarity annotation rather than a measurement. The first, non-catalytic domain is conventionally called the pseudokinase or JH2 domain, and it negatively regulates the adjacent kinase domain; crystal structures describe it as adopting the fold of a prototypical protein kinase and binding magnesium-ATP noncanonically, so “pseudokinase” means catalytically inert by role, not structurally unlike a kinase. That matters for V617F, the most prevalent mutant in myeloproliferative neoplasms, which is annotated as causing constitutive tyrosine phosphorylation activity that promotes cytokine hypersensitivity and is reported to rigidify helix alpha-C in the N lobe of that domain. Residue 617 sits inside the 545 to 809 range, placing it in the regulatory domain rather than the catalytic one: the mutation breaks a brake rather than sharpening a blade. Those boundaries were read for JAK2 alone and should not be generalised to the other three.
The growth-hormone arm
This is the part of the pathway that matters most to anyone reading growth-hormone literature, and also where it is most often described loosely.
The growth hormone receptor is a type I cytokine receptor, and on ligand binding it couples to the JAK2/STAT5 pathway: it forms homodimers and binds JAK2 via a box 1-containing domain. The exclusivity is explicit in the review literature — for the growth hormone receptor, the only JAK family member that binds the receptor is JAK2. Downstream, STAT5 is described as the predominant transcription factor that delivers growth hormone-induced cell proliferation and actions, and postnatal growth in mice has been shown to rely on signalling mediated by JAK2 and STAT5.
Within STAT5 the division of labour is uneven, and the mouse and human genetics agree. Mice lacking STAT5b are not growth hormone-deficient, which suggested to the original investigators that they may be growth hormone pulse-resistant; those authors concluded that STAT5b has unique physiological functions for which, surprisingly, the highly homologous STAT5a is unable to substitute. In people, dominant-negative STAT5B mutations cause growth hormone insensitivity with short stature and mild immune dysregulation: severe postnatal growth failure that does not respond to exogenous growth hormone administration, with normal or elevated growth hormone secretion and severe IGF-1 and IGFBP-3 deficiency that does not rise when growth hormone is given. Insensitivity, not deficiency, is the accurate framing, and it matches “pulse-resistant” in the mouse work.
IGF-1 is the output usually drawn at the end of this chain, and the evidence type is worth stating exactly. Multiple evolutionarily conserved growth hormone-activated chromosomal binding domains for Stat5b have been characterised within the rat Igf1 locus, each containing two or three Stat5b recognition sequences able to bind Stat5b in vitro. That is direct biochemical demonstration in the rat gene; conserved human regions were mapped, but this article does not assert a demonstration of direct STAT5B binding to the human IGF1 locus. And growth hormone signalling is not exclusively JAK2/STAT5 in any case: growth hormone can activate Src-family kinases independently of any JAK2 activation, a process that results in RAS activation and initiation of the ERK1/2 pathway, and PI 3-kinase and Akt are also activated by the receptor. A single linear chain from growth hormone to JAK2 to STAT5B to IGF-1 is a useful teaching diagram, not a complete account.
How the pathway switches itself off
A pathway this short needs strong brakes, and the wiring of the main one is the elegant part: STATs, along with NF-kB, can bind regulatory elements within the promoters of the socs1 and socs3 genes, so the signal transcribes its own inhibitor. The suppressor of cytokine signalling family has eight human members, SOCS1 to SOCS7 and CIS. The founding 1997 paper reported that SOCS-1 expression inhibited both interleukin-6-induced receptor phosphorylation and STAT activation, suggesting these proteins may act in a classic negative feedback loop — a suggestion in the authors’ own framing, describing induction by interleukin-6 rather than by STATs directly. Mechanistically, SOCS1 binds a JAK using both its SH2 domain and a kinase inhibitory region of about twelve residues that acts as a pseudosubstrate, blocking the kinase’s substrate-binding groove: competitive inhibition by impersonation.
SOCS2 is the brake on the growth-hormone arm specifically, and its knockout is a giant. Mice lacking SOCS2 grew significantly larger than their wild-type littermates, with increased long bone lengths, proportionate enlargement of most organs and increased local IGF-1 production, indicating that SOCS-2 may have an essential negative regulatory role in the growth hormone and IGF-1 pathway — again the authors’ own hedge. A later study put the effect at a 30 to 50 per cent increase in mature body size and established that growth hormone signalling is required for the phenotype to develop; the loop closes because STAT5b is required for the induction of SOCS-2 and SOCS-3 in liver, a tissue-specific result, since the same work reports STAT5b loss did not affect growth hormone-induced CIS and SOCS-2 in mammary gland. One caution against simplifying: the SOCS2 reporter data are biphasic, with low levels inhibiting about half of signalling while higher levels led to a recovery or enhancement of signal.
Two further restraints act on different steps. The phosphatases SHP-1 and SHP-2 were among the first negative regulators of JAK signalling identified and directly dephosphorylate JAKs and their associated receptors, as does PTP1B — in work its authors scoped to interleukin-6 signalling in one macrophage cell line, not to tissue generally. The PIAS family, PIAS1 to PIAS4, instead counteracts STAT activity by binding active STAT dimers and blocking DNA binding: inhibition at the last step rather than the first.
What human genetics reveals
The strongest evidence that each component matters is what happens when one is missing. These are inherited human conditions, described as biology; nothing here concerns any product.
| Component | Consequence reported | What it demonstrates |
|---|---|---|
| JAK3 | Two unrelated patients with T-cell-negative, B-cell-positive SCID, homozygous JAK3 mutations and markedly reduced JAK3 levels | A single kinase is non-redundant for lymphocyte development |
| Shared gamma chain (IL2RG) | X-linked SCID, through to atypical presentations | Its tail constitutively associates with JAK3, and the chain is shared across the IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21 receptors — the firmest receptor-to-JAK pairing available |
| STAT3 | Hyper-IgE syndrome: highly elevated serum IgE, recurrent staphylococcal skin abscesses and cyst-forming pneumonia, plus skeletal abnormalities | The mutations are dominant-negative and sit in the DNA-binding domain, which is why one bad copy suffices |
| STAT5B | Growth hormone insensitivity with short stature and mild immune dysregulation, in both recessive and dominant forms | The growth-hormone arm is non-redundant in people, and its failure looks like resistance |
STAT1 belongs on that list too: its deficiency causes an impaired response to interferon-alpha and interferon-beta with lethal viral disease. This article makes no claim about the mycobacterial side of the STAT1 story, which it could not verify. And because the kinase step is enzymatic, it is also the druggable one: several JAK inhibitors are approved prescription medicines, from ruxolitinib, whose label says it “inhibits Janus Associated Kinases (JAKs), JAK1 and JAK2”, to deucravacitinib, which “binds to the regulatory domain of TYK2, stabilizing an inhibitory interaction”. Each of those labels also states that the relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known — a pathway can be well understood and deliberately targeted while the reason the targeting works remains open. Two further corrections from reading the labels rather than the summaries: it is not true that all JAK inhibitors carry a boxed warning, since two of the six retrieved had none, and tofacitinib is often called a selective JAK3 inhibitor, which its own label does not support.
Where GH-axis peptides actually act
If you arrived here from growth-hormone research, this is the section that matters, and the answer is a clean negative: the compounds most often discussed in that context do not act on the JAK-STAT pathway. They act one step earlier, on the pituitary, through different receptor families. The pathway is downstream context, not a target.
| Compound | The receptor it acts at | Relationship to JAK-STAT |
|---|---|---|
| Sermorelin | GHRH(1-29)-amide, the biologically active fragment of human growth hormone-releasing factor. It binds the GHRH receptor, coupled to G proteins which activate adenylyl cyclase, in the G protein-coupled receptor 2 family | None. The GHRH receptor carries no JAK or STAT annotation and is not a type I cytokine receptor |
| CJC-1295 with DAC | A long-acting GHRH analogue, so the same receptor. Its best human evidence is two randomised, placebo-controlled, double-blind ascending-dose trials in healthy adults aged 21 to 61, measuring growth hormone and IGF-1 secretion; three of that paper’s six authors were affiliated with the company that developed it | None at its own receptor. Any STAT5 involvement would be downstream of the growth hormone those studies measured, and they did not measure it |
| CJC-1295 without DAC | A published 2026 review states plainly that it “remains essentially uncharacterised in the peer-reviewed human literature” and that “no controlled clinical studies have directly evaluated this compound in humans” | None established, and here there is no human characterisation to reason from at all |
| Ipamorelin | An agonist at the ghrelin receptor GHSR1a, which is coupled to Gq proteins and mediates production of diacylglycerol and inositol 1,4,5-trisphosphate | None. A different G protein-coupled receptor again, and a different second messenger from the GHRH receptor |
| IGF-1 LR3 | An IGF-1 analogue acting at the IGF-1 receptor, a receptor tyrosine kinase whose principal cascades are PI3K-AKT and MAPK | Not a JAK2/STAT5B cytokine-receptor chain — but the curated entry records a secondary route: the IGF-1 receptor also signals through the JAK/STAT pathway, with STAT3 in particular. It is STAT3, not STAT5B, and nothing specific to the LR3 analogue was verified |
The strongest statement this article can make is a search result rather than a measurement, and its limits are worth stating. Looking for published work measuring JAK2, STAT5 or STAT5B phosphorylation, or SOCS expression, after administration of these compounds: we could find no such study for sermorelin, and none for ipamorelin. For CJC-1295, with or without DAC, we could find none either, but that search was less complete, so treat it as the weaker of the three findings. In every case the primary literature that does measure these markers measured them after growth hormone itself, not after a secretagogue.
A correction to our own earlier wording. An earlier article on this site stated that a dedicated review calls the GHSR1a-to-cyclic-AMP route “debated”. We could not re-verify that, because the pharmacology database it came from now requires a login. The readable review we did find says instead that in isolation, under defined conditions, GHSR1a couples to G-alpha-q resulting in activation of phospholipase C, and notes a separate G-alpha-i route in one context. The accurate state of play is Gq/11 as the canonical coupling with a documented Gi route in at least one setting.
Growth and signalling research reagents are stocked as laboratory materials, priced in CAD.
Browse growth & signalingWhat’s established and what isn’t
Reasonably well established
- Ligand binding brings cytokine receptor chains together; the attached JAKs cross-phosphorylate, then phosphorylate the receptor tails, which STATs read through SH2 domains.
- STATs are activated at a single tyrosine near the C-terminus, and that phosphorylation is required for dimerisation, DNA binding and nuclear entry.
- The growth hormone receptor is a type I cytokine receptor and JAK2 is the only JAK that binds it.
- Losing JAK3 or the shared gamma chain causes severe combined immunodeficiency; dominant-negative STAT5B mutations cause growth hormone insensitivity.
- SOCS proteins are transcriptional targets of the pathway and inhibit it; SOCS2 knockout mice are larger, and that phenotype requires growth hormone signalling.
Open questions
- A complete, traceable mapping of every cytokine receptor class to its JAK pair. Published reviews do not agree on one, and the type I versus type II definition is stated inconsistently.
- Which kinase phosphorylates STAT3 at Tyr-705 and STAT5B at Tyr-699 in a given tissue. The curated annotations do not attribute those sites to JAKs.
- Exactly how the JAK2 pseudokinase domain restrains the adjacent kinase domain. The structural work describes the restraint, not a settled mechanism.
- Whether direct STAT5B binding to the human IGF1 locus mirrors what has been demonstrated in the rat gene.
- Whether any growth hormone secretagogue measurably changes JAK2, STAT5 or SOCS activity in people. No study we could find has asked.
Sourcing GH-axis research reagents in Canada
The documentation questions here are the ordinary ones, with one caveat this article has spent several sections earning: check that the mechanism you intend to study matches the receptor the compound actually acts on, because a GHRH analogue and a ghrelin-receptor agonist are not interchangeable, and neither is a cytokine-receptor ligand.
- Match the identity test to the molecule. A 29-residue fragment and a pentapeptide are different analytical problems from an 83-residue analogue. Our guides to reading a certificate of analysis and what grade labels do and don’t mean cover what a useful document contains.
- Match the batch number on the report to the number on your vial. A certificate describes the material that was tested and nothing else.
- Read the primary literature for the receptor, not the marketing for the pathway. How to read a peptide study sets out what cell, animal and human work can each support.
- Know which blend you have. Co-formulated vials raise their own verification questions, covered in what’s in a blended vial.
SermorelinGHRH(1-29)-amide — acts at the GHRH receptor, upstream of this pathwayView product
CJC-1295 with DACThe albumin-binding GHRH analogue with published human pharmacokinetic dataView product
IpamorelinA GHSR1a agonist — a Gq-coupled receptor, not a cytokine receptorView product
IGF-1 LR3Acts at a receptor tyrosine kinase; a secondary JAK/STAT3 route is annotated for itView product
Research use only. Pure Peptides Canada products are laboratory reagents for in-vitro research, not for human or veterinary use. This article explains published research for education; it is not medical, dietary or dosing guidance.
Frequently asked questions
What is the JAK-STAT pathway?
The JAK-STAT pathway is the route by which a cytokine or hormone binding outside a cell changes which genes are transcribed inside it, in only a few steps. Binding brings receptor chains close together; the Janus kinases on their tails phosphorylate each other and then the tails themselves; STAT proteins dock onto those phosphorylated tails through SH2 domains and are each phosphorylated on a single tyrosine near the C-terminus; the phosphorylated STATs pair up, enter the nucleus and bind DNA. There is no second messenger and no tier structure, which is why it is often called the shortest route from a receptor to a gene.
What do JAK and STAT stand for?
JAK stands for Janus kinase and STAT for signal transducer and activator of transcription. Humans have four JAKs: JAK1, JAK2, JAK3 and TYK2. TYK2’s approved gene name is simply tyrosine kinase 2 and does not contain the word Janus, so although the four Janus kinases is accepted family shorthand, TYK2 should never be written as Janus kinase 4. Seven human genes encode STAT proteins.
How does growth hormone use the JAK-STAT pathway?
The growth hormone receptor is a type I cytokine receptor, and JAK2 is the only JAK family member that binds it. Growth hormone binding leads to receptor homodimers, JAK2 activation and then STAT5 phosphorylation, and STAT5 is described as the predominant transcription factor delivering growth hormone’s effects on cell proliferation. This chain runs in peripheral tissues such as the liver, downstream of growth hormone itself, not in the pituitary where growth hormone is released.
Do sermorelin, CJC-1295 or ipamorelin act on JAK-STAT?
No. Sermorelin is the 1-29 fragment of growth hormone-releasing hormone and acts at the GHRH receptor, a G protein-coupled receptor that activates adenylyl cyclase; CJC-1295 is a long-acting GHRH analogue at the same receptor; ipamorelin acts at the ghrelin receptor GHSR1a, which couples to Gq proteins and phospholipase C. None of those receptors carries any JAK or STAT annotation. We could find no published study measuring JAK2, STAT5 or STAT5B phosphorylation, or SOCS expression, after administration of sermorelin or ipamorelin.
What are SOCS proteins and what do they do?
SOCS stands for suppressor of cytokine signalling, and the human family has eight members: SOCS1 to SOCS7 plus CIS. They are the pathway’s own brake, and the wiring is the elegant part: STATs can bind regulatory elements in the promoters of SOCS genes, so the signal switches on the genes that shut it down. SOCS2 is the brake on the growth-hormone arm: mice lacking it grew significantly larger than their wild-type littermates, and that phenotype requires growth hormone signalling to develop.
Why are there JAK inhibitors but no STAT inhibitors?
Because the kinase step is the enzymatic, druggable one. Several JAK inhibitors are approved prescription medicines and their labels state which kinases they inhibit, from ruxolitinib acting on JAK1 and JAK2 to deucravacitinib binding the regulatory domain of TYK2 to inhibit it allosterically. Each of those labels also carries its own statement that the relevance of inhibiting specific JAK enzymes to therapeutic effectiveness is not currently known. They are named here only as pathway context; nothing in this catalogue is a medicine.
Growth and signalling reagents, documented by batch
Sermorelin, the CJC-1295 forms, ipamorelin and IGF-1 LR3, priced in Canadian dollars and shipped tracked from inside Canada.
References
- Darnell JE Jr, Kerr IM, Stark GR. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science. 1994;264(5164):1415–1421. DOI (cited for its title, authorship and framing only)
- Albert and Mary Lasker Foundation. 2002 Albert Lasker Special Achievement Award in Medical Science: James E. Darnell Jr. laskerfoundation.org
- Majoros A, Platanitis E, Kernbauer-Hölzl E, Rosebrock F, Müller M, Decker T. Canonical and non-canonical aspects of JAK-STAT signaling: lessons from interferons for cytokine responses. Front Immunol. 2017;8:29. DOI
- Hu X, Li J, Fu M, et al. The JAK/STAT signaling pathway: from bench to clinic. Signal Transduct Target Ther. 2021;6:402. DOI (author list truncated on the publisher page)
- UniProt Consortium. UniProtKB entries P42224 (STAT1), P40763 (STAT3), P42229 (STAT5A), P51692 (STAT5B), O60674 (JAK2), P10912 (GHR), Q02643 (GHRHR), Q92847 (GHSR) and P08069 (IGF1R). uniprot.org
- HUGO Gene Nomenclature Committee. Records HGNC:6190 (JAK1), HGNC:6192 (JAK2), HGNC:6193 (JAK3), HGNC:12440 (TYK2) and HGNC:11362–11368 (STAT1–STAT6). genenames.org
- Bandaranayake RM, Ungureanu D, Shan Y, Shaw DE, Silvennoinen O, Hubbard SR. Crystal structures of the JAK2 pseudokinase domain and the pathogenic mutant V617F. Nat Struct Mol Biol. 2012;19(8):754–759. DOI (abstract and figure legends only)
- Perner F, Pahl HL, Zeiser R, et al. Malignant JAK-signaling: at the interface of inflammation and malignant transformation. Leukemia. 2025;39(5):1011–1030. DOI
- Morelli M, Madonna S, Albanesi C. SOCS1 and SOCS3 as key checkpoint molecules in the immune responses associated to skin inflammation and malignant transformation. Front Immunol. 2024;15:1393799. DOI
- Starr R, Willson TA, Viney EM, et al. A family of cytokine-inducible inhibitors of signalling. Nature. 1997;387(6636):917–921. DOI (abstract only)
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- Dehkhoda F, Lee CMM, Medina J, Brooks AJ. The growth hormone receptor: mechanism of receptor activation, cell signaling, and physiological aspects. Front Endocrinol. 2018;9:35. DOI
- Udy GB, Towers RP, Snell RG, et al. Requirement of STAT5b for sexual dimorphism of body growth rates and liver gene expression. Proc Natl Acad Sci USA. 1997;94(14):7239–7244. DOI (abstract only)
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- Klammt J, Neumann D, Gevers EF, et al. Dominant-negative STAT5B mutations cause growth hormone insensitivity with short stature and mild immune dysregulation. Nat Commun. 2018;9:2105. DOI
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- Davey HW, McLachlan MJ, Wilkins RJ, Hilton DJ, Adams TE. STAT5b mediates the GH-induced expression of SOCS-2 and SOCS-3 mRNA in the liver. Mol Cell Endocrinol. 1999;158(1-2):111–116. DOI (abstract only)
- Macchi P, Villa A, Giliani S, et al. Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID). Nature. 1995;377(6544):65–68. DOI (abstract only)
- Briassouli E, Marinakis N, Spoulou V, Notarangelo LD. IL2RG-related immunodeficiencies: from SCID to atypical presentations. Front Immunol. 2026;17:1703097. DOI
- Dupuis S, Jouanguy E, Al-Hajjar SH, et al. Impaired response to interferon-alpha/beta and lethal viral disease in human STAT1 deficiency. Nat Genet. 2003;33(3):388–391. DOI (title and metadata only; cited for the viral finding named in its title)
- Minegishi Y, Saito M, Tsuchiya S, et al. Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature. 2007;448(7157):1058–1062. DOI (abstract and figure legends only)
- Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne J-P, Frohman LA. Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab. 2006;91(3):799–805. DOI (abstract and Crossref metadata only)
- Dominikowski A, Rękoś Z, Olejarz M, et al. The emerging landscape of performance-enhancing peptides modulating GH-IGF1 axis: bridging the gap between clinical evidence and patient self-administration. Front Endocrinol. 2026;17:1822475. DOI
- Kern A, Grande C, Smith RG. Apo-ghrelin receptor (apo-GHSR1a) regulates dopamine signaling in the brain. Front Endocrinol. 2014;5:129. DOI
- National Center for Biotechnology Information. PubChem compound summary CID 16129620, sermorelin. pubchem.ncbi.nlm.nih.gov
- US Food and Drug Administration. Prescribing information for JAKAFI (ruxolitinib), XELJANZ (tofacitinib), OLUMIANT (baricitinib), RINVOQ (upadacitinib), CIBINQO (abrocitinib) and SOTYKTU (deucravacitinib). accessdata.fda.gov
For laboratory research use only. Not for human or veterinary use. This article summarizes published research for educational purposes and is not medical advice.
