Related Experiment Video

Updated: Aug 8, 2026

Antibody Binding Specificity for Kappa (Vκ) Light Chain-containing Human (IgM) Antibodies: Polysialic Acid (PSA) Attached to NCAM as a Case Study
11:10

Antibody Binding Specificity for Kappa (Vκ) Light Chain-containing Human (IgM) Antibodies: Polysialic Acid (PSA) Attached to NCAM as a Case Study

Published on: June 29, 2016

The kangaroo cation-independent mannose 6-phosphate receptor binds insulin-like growth factor II with low affinity

C A Yandell1, A J Dunbar, J F Wheldrake

  • 1Cooperative Research Centre for Tissue Growth and Repair, P. O. Box 10065, Adelaide B.C., South Australia, Australia, 5000. catherine.yandell@imvs.sa.gov.au

The Journal of Biological Chemistry
|September 10, 1999
PubMed

Insights

The kangaroo cation-independent mannose 6-phosphate receptor (CI-MPR) binds insulin-like growth factor (IGF)-II with lower affinity than placental mammals. This marsupial CI-MPR shows higher affinity for kangaroo IGF-II, suggesting recent evolution of high-affinity binding in eutherians.

Area of Science:

  • Molecular biology
  • Comparative genomics
  • Receptor-ligand interactions

Background:

  • The mammalian cation-independent mannose 6-phosphate receptor (CI-MPR) is known to bind mannose 6-phosphate-bearing glycoproteins and insulin-like growth factor (IGF)-II.
  • Previous studies indicated low affinity binding of bovine IGF-II to opossum CI-MPR, necessitating investigation in a homologous system.
  • Understanding CI-MPR-IGF-II interactions is crucial for elucidating IGF-II regulation across mammalian evolution.

Purpose of the Study:

  • To investigate the binding affinity of marsupial CI-MPR to IGF-II in a homologous system.
  • To characterize the kangaroo CI-MPR and its interaction with kangaroo and human IGF-II.
  • To explore the evolutionary divergence of the IGF-II binding site in CI-MPR.

Main Methods:

  • Purification of kangaroo liver CI-MPR and kangaroo IGF-II.
  • Ligand blotting and radioreceptor assays to assess binding.
  • Real-time biomolecular interaction analysis (SPR) for kinetic characterization.
  • Analysis of kangaroo CI-MPR cDNA sequence.

Main Results:

  • Kangaroo CI-MPR exhibits lower binding affinity for IGF-II compared to eutherian (placental mammal) CI-MPRs.
  • Real-time analysis shows higher affinity of kangaroo CI-MPR for kangaroo IGF-II than for human IGF-II.
  • Kangaroo CI-MPR cDNA sequence reveals significant divergence in the IGF-II binding region compared to eutherian receptors.

Conclusions:

  • The binding affinity of CI-MPR for IGF-II differs between marsupials and eutherians.
  • The evolution of a high-affinity IGF-II binding site appears to be a recent event specific to the eutherian lineage.
  • These findings provide insights into the molecular evolution of IGF-II regulation.

More Related Videos

Automated Imaging and Analysis for the Quantification of Fluorescently Labeled Macropinosomes11:01

Automated Imaging and Analysis for the Quantification of Fluorescently Labeled Macropinosomes

Published on: August 24, 2021

Precise Visualization of Insulin Receptors A and B in Murine Brain with an RNA In Situ Hybridization Assay08:34

Precise Visualization of Insulin Receptors A and B in Murine Brain with an RNA In Situ Hybridization Assay

Published on: July 15, 2025

Related Concept Videos

Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but this inhibition is released...