GHBP Human, His

Growth Hormone Binding Protein Human Recombinant, His Tag
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Description

Functional Role in GH Signaling

GHBP Human, His binds GH with high affinity, forming a 1:1 complex that regulates GH bioavailability and receptor interactions .

Key Mechanisms

  • Receptor Dimerization: GH binding induces dimerization of the growth hormone receptor (GHR), activating JAK2/STAT5 signaling .

  • Modulation of GH Half-Life: GHBP prolongs GH’s circulation by reducing its clearance rate .

  • Competitive Inhibition: High GHBP concentrations inhibit GH binding to GHR, acting as a regulatory feedback mechanism .

Binding Stoichiometry

GH:GHBP ComplexRatioFunction
1:1DominantTransport and stabilization of GH
1:2RareAntagonistic effects at high GHBP levels

Diagnostic Utility

GHBP levels correlate with GHR expression and are used to assess growth disorders:

ConditionGHBP Levels (pmol/L)Clinical Relevance
Healthy Adults~287.9 (9–12 years) Baseline for growth hormone insensitivity
Idiopathic Short Stature122.4 ± 11.0 Reduced GHBP linked to GH insensitivity
Hypopituitarism157.1 ± 23.0 Altered GH/GHBP dynamics in pituitary disorders

Isoform Variability

Exon 3 splicing generates two GHBP isoforms:

  • E3+: Includes exon 3 (dominant in males).

  • E3-: Exon 3 deleted (higher in females) .

IsoformExon 3 StatusAmino AcidsFunction
E3+Included246 aaFull-length extracellular domain
E3-Excluded~230 aaTruncated domain; unclear role

Expression Systems

SystemGlycosylationMolecular WeightKey Features
Sf9 Insect CellsYes 29.4 kDa Native post-translational modifications
E. coliNo 28.1 kDa Lower cost but non-glycosylated

Developmental Trends

GHBP levels rise sharply postnatally:

  • Newborns: Undetectable .

  • 2 Months–2 Years: Rapid increase .

  • Puberty: Slower increase .

Correlation with Growth Metrics

FactorEffect on GHBPImplication
Standardized WeightPositive correlation GHBP linked to adiposity and growth velocity
Height SDSNegative correlation Possible role in GH-independent growth regulation

Product Specs

Introduction
The growth hormone receptor (GHR) belongs to the cytokine receptor family. Upon binding two GHR molecules, growth hormone triggers signal transduction via receptor dimerization. However, at elevated concentrations, growth hormone exhibits antagonist properties due to the significant disparity in binding affinities at its respective binding sites. This antagonistic effect can be further amplified by diminishing binding at the low-affinity binding site.
Description
Produced in Sf9 insect cells, GHBP is a single, glycosylated polypeptide chain comprising 254 amino acids (19-264a.a.) with a molecular mass of 29.4 kDa. It features an 8-amino acid His tag at the C-terminus and is purified using proprietary chromatographic techniques.
Physical Appearance
A sterile, colorless solution that has been filtered.
Formulation
The GHBP protein solution is provided at a concentration of 1 mg/ml and contains phosphate-buffered saline (pH 7.4) and 10% glycerol.
Stability
For short-term storage (2-4 weeks), the product should be kept at 4°C. For extended storage, it is recommended to freeze the product at -20°C. The addition of a carrier protein (0.1% HSA or BSA) is advisable for long-term storage. Repeated freeze-thaw cycles should be avoided.
Purity
The purity of GHBP is greater than 95.0% as determined by SDS-PAGE analysis.
Biological Activity
The ED50 value, representing the effective concentration for 50% activity, is approximately 10 ng/ml. This is assessed by measuring the ability of GHBP to inhibit GH-induced proliferation in Nb2-11 rat lymphoma cells in the presence of 1.25 ng/ml human growth hormone.
Synonyms
Growth Hormone Receptor, Growth Hormone Binding Protein, Somatotropin Receptor GH Receptor, Serum Binding Protein, GHBP, GHIP.
Source
Sf9, Insect cells.
Amino Acid Sequence
FSGSEATAAI LSRAPWSLQS VNPGLKTNSS KEPKFTKCRS PERETFSCHW TDEVHHGTKN LGPIQLFYTR RNTQEWTQEW KECPDYVSAG ENSCYFNSSF TSIWIPYCIK LTSNGGTVDE KCFSVDEIVQ PDPPIALNWT LLNVSLTGIH ADIQVRWEAP RNADIQKGWM VLEYELQYKE
VNETKWKMMD PILTTSVPVY SLKVDKEYEV RVRSKQRNSG NYGEFSEVLY VTLPQMSQFT CEEDFYLEHH HHHH.

Product Science Overview

Structure and Function

GHBP is a glycoprotein that binds to GH with high affinity, preventing its degradation and prolonging its half-life in the bloodstream. This binding also regulates the amount of free GH available to interact with cell surface receptors, thereby modulating GH signaling pathways. The interaction between GH and GHBP is essential for maintaining proper growth and metabolic functions.

Recombinant GHBP Production

Recombinant GHBP is produced using various expression systems, including bacterial, yeast, insect, and mammalian cells. The human recombinant GHBP with a His tag is commonly expressed in Escherichia coli (E. coli) due to its simplicity and cost-effectiveness. The His tag, a sequence of histidine residues, is added to the protein to facilitate its purification using affinity chromatography techniques.

Expression and Purification

The production of recombinant GHBP involves several steps:

  1. Gene Cloning: The gene encoding the extracellular domain of the human GHR is cloned into an expression vector that includes a sequence for the His tag.
  2. Transformation: The expression vector is introduced into E. coli cells, which then produce the recombinant GHBP.
  3. Induction: The expression of GHBP is induced using specific chemicals, such as IPTG (isopropyl β-D-1-thiogalactopyranoside).
  4. Harvesting: The bacterial cells are harvested and lysed to release the recombinant protein.
  5. Purification: The His-tagged GHBP is purified using nickel affinity chromatography, which selectively binds to the His tag, allowing for the isolation of the recombinant protein.
Applications

Recombinant GHBP is used in various research and clinical applications, including:

  • Studying GH Signaling: GHBP is used to investigate the mechanisms of GH signaling and its regulation.
  • Therapeutic Development: GHBP can be used in the development of therapeutic agents for conditions related to GH deficiency or excess.
  • Diagnostic Tools: GHBP is utilized in diagnostic assays to measure GH levels and assess GH-related disorders.

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