How does the mitogenic insulin-like growth factor I receptor differ from the metabolic insulin receptor?

D. LeRoith, P. C. Sampson, Charles Roberts

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Under normal physiological conditions, insulin regulates intermediary metabolism by interacting with insulin receptors in liver, fat and muscle cells. The insulin-like growth factors (IGF-I and IGF-II), on the other hand, are primarily involved in the regulation of growth and development of the whole organism and interact with IGF receptors expressed by most, if not all, tissues of the body. As the insulin and IGF-I receptors are both structurally and functionally similar, one of the fundamental questions in this area of research has been the basis for the distinct pathways of hormone action elicited by insulin and the IGFs. Several features are involved in the divergence of the signalling pathways of insulin and the IGFs. The insulin receptor binds insulin with high affinity, and this specificity is determined by domains lying to the N- terminal and C-terminal sides of the cysteine-rich region in the α-subunit. The high-affinity IGF binding by the IGF-I receptor is determined by its cysteine-rich domain. Secondly, the IGF-binding proteins (IGFBPs), of which six have been characterized, bind the IGFs with an affinity higher than that of the IGF receptors. They bind all the circulating IGFs, protect them from degradation and deliver them to the IGF receptors in the target tissues, where they modulate IGF action. As they have no affinity for insulin, insulin is free to interact with its own receptor. Finally, structural differences in the β-subunits of the insulin and IGF-I receptors may result in divergence of the signal pathways. Although both receptors have similar tyrosine kinase domains, their C-terminal domains, for example, differ. Recent studies have suggested that these structural differences may be causally related to their different signalling pathways.

Original languageEnglish (US)
Pages (from-to)74-78
Number of pages5
JournalHormone Research
Volume41
Issue numberSUPPL. 2
StatePublished - 1994
Externally publishedYes

Fingerprint

IGF Type 1 Receptor
Insulin Receptor
Insulin
Insulin-Like Growth Factor I
Cysteine
Insulin-Like Growth Factor Binding Proteins
Insulin-Like Growth Factor II
Growth and Development
Adipocytes
Protein-Tyrosine Kinases
Muscle Cells
Signal Transduction
Hormones
Liver

Keywords

  • Insulin receptor
  • Insulin-like growth factor binding proteins
  • Insulin-like growth factor I receptor
  • Ligand-receptor interactions
  • Subunit structure

ASJC Scopus subject areas

  • Endocrinology

Cite this

How does the mitogenic insulin-like growth factor I receptor differ from the metabolic insulin receptor? / LeRoith, D.; Sampson, P. C.; Roberts, Charles.

In: Hormone Research, Vol. 41, No. SUPPL. 2, 1994, p. 74-78.

Research output: Contribution to journalArticle

@article{55517f142f2e4e6dadcdb90df24f8176,
title = "How does the mitogenic insulin-like growth factor I receptor differ from the metabolic insulin receptor?",
abstract = "Under normal physiological conditions, insulin regulates intermediary metabolism by interacting with insulin receptors in liver, fat and muscle cells. The insulin-like growth factors (IGF-I and IGF-II), on the other hand, are primarily involved in the regulation of growth and development of the whole organism and interact with IGF receptors expressed by most, if not all, tissues of the body. As the insulin and IGF-I receptors are both structurally and functionally similar, one of the fundamental questions in this area of research has been the basis for the distinct pathways of hormone action elicited by insulin and the IGFs. Several features are involved in the divergence of the signalling pathways of insulin and the IGFs. The insulin receptor binds insulin with high affinity, and this specificity is determined by domains lying to the N- terminal and C-terminal sides of the cysteine-rich region in the α-subunit. The high-affinity IGF binding by the IGF-I receptor is determined by its cysteine-rich domain. Secondly, the IGF-binding proteins (IGFBPs), of which six have been characterized, bind the IGFs with an affinity higher than that of the IGF receptors. They bind all the circulating IGFs, protect them from degradation and deliver them to the IGF receptors in the target tissues, where they modulate IGF action. As they have no affinity for insulin, insulin is free to interact with its own receptor. Finally, structural differences in the β-subunits of the insulin and IGF-I receptors may result in divergence of the signal pathways. Although both receptors have similar tyrosine kinase domains, their C-terminal domains, for example, differ. Recent studies have suggested that these structural differences may be causally related to their different signalling pathways.",
keywords = "Insulin receptor, Insulin-like growth factor binding proteins, Insulin-like growth factor I receptor, Ligand-receptor interactions, Subunit structure",
author = "D. LeRoith and Sampson, {P. C.} and Charles Roberts",
year = "1994",
language = "English (US)",
volume = "41",
pages = "74--78",
journal = "Hormone Research in Paediatrics",
issn = "1663-2818",
publisher = "S. Karger AG",
number = "SUPPL. 2",

}

TY - JOUR

T1 - How does the mitogenic insulin-like growth factor I receptor differ from the metabolic insulin receptor?

AU - LeRoith, D.

AU - Sampson, P. C.

AU - Roberts, Charles

PY - 1994

Y1 - 1994

N2 - Under normal physiological conditions, insulin regulates intermediary metabolism by interacting with insulin receptors in liver, fat and muscle cells. The insulin-like growth factors (IGF-I and IGF-II), on the other hand, are primarily involved in the regulation of growth and development of the whole organism and interact with IGF receptors expressed by most, if not all, tissues of the body. As the insulin and IGF-I receptors are both structurally and functionally similar, one of the fundamental questions in this area of research has been the basis for the distinct pathways of hormone action elicited by insulin and the IGFs. Several features are involved in the divergence of the signalling pathways of insulin and the IGFs. The insulin receptor binds insulin with high affinity, and this specificity is determined by domains lying to the N- terminal and C-terminal sides of the cysteine-rich region in the α-subunit. The high-affinity IGF binding by the IGF-I receptor is determined by its cysteine-rich domain. Secondly, the IGF-binding proteins (IGFBPs), of which six have been characterized, bind the IGFs with an affinity higher than that of the IGF receptors. They bind all the circulating IGFs, protect them from degradation and deliver them to the IGF receptors in the target tissues, where they modulate IGF action. As they have no affinity for insulin, insulin is free to interact with its own receptor. Finally, structural differences in the β-subunits of the insulin and IGF-I receptors may result in divergence of the signal pathways. Although both receptors have similar tyrosine kinase domains, their C-terminal domains, for example, differ. Recent studies have suggested that these structural differences may be causally related to their different signalling pathways.

AB - Under normal physiological conditions, insulin regulates intermediary metabolism by interacting with insulin receptors in liver, fat and muscle cells. The insulin-like growth factors (IGF-I and IGF-II), on the other hand, are primarily involved in the regulation of growth and development of the whole organism and interact with IGF receptors expressed by most, if not all, tissues of the body. As the insulin and IGF-I receptors are both structurally and functionally similar, one of the fundamental questions in this area of research has been the basis for the distinct pathways of hormone action elicited by insulin and the IGFs. Several features are involved in the divergence of the signalling pathways of insulin and the IGFs. The insulin receptor binds insulin with high affinity, and this specificity is determined by domains lying to the N- terminal and C-terminal sides of the cysteine-rich region in the α-subunit. The high-affinity IGF binding by the IGF-I receptor is determined by its cysteine-rich domain. Secondly, the IGF-binding proteins (IGFBPs), of which six have been characterized, bind the IGFs with an affinity higher than that of the IGF receptors. They bind all the circulating IGFs, protect them from degradation and deliver them to the IGF receptors in the target tissues, where they modulate IGF action. As they have no affinity for insulin, insulin is free to interact with its own receptor. Finally, structural differences in the β-subunits of the insulin and IGF-I receptors may result in divergence of the signal pathways. Although both receptors have similar tyrosine kinase domains, their C-terminal domains, for example, differ. Recent studies have suggested that these structural differences may be causally related to their different signalling pathways.

KW - Insulin receptor

KW - Insulin-like growth factor binding proteins

KW - Insulin-like growth factor I receptor

KW - Ligand-receptor interactions

KW - Subunit structure

UR - http://www.scopus.com/inward/record.url?scp=0028352022&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028352022&partnerID=8YFLogxK

M3 - Article

VL - 41

SP - 74

EP - 78

JO - Hormone Research in Paediatrics

JF - Hormone Research in Paediatrics

SN - 1663-2818

IS - SUPPL. 2

ER -