Differential phosphorylation of pp120 by insulin and insulin-like growth factor-I receptors

Role for the C-terminal domain of the β-subunit

Sonia M. Najjar, Vicky A. Blakesley, Sergio Li Calzi, Hisanori Kato, Derek LeRoith, Curtis Choice

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

pp120, a plasma membrane glycoprotein expressed by hepatocytes, is a substrate of the insulin receptor tyrosine kinase. Since insulin-like growth factor-1 (IGF-1) and insulin receptors are structurally homologous, we investigated whether pp120 is also a substrate of the IGF-1 receptor tyrosine kinase. IGF-1 receptor failed to phosphorylate pp120 in response to IGF-1 in stably transfected NIH 3T3 fibroblasts. However, replacement of the C- terminal domain of the β-subunit of the IGF-1 receptor with the corresponding fragment in the insulin receptor restored ligand-stimulated pp120 phosphorylation, suggesting that this domain plays a regulatory role in pp120 phosphorylation. Since pp120 is the first identified substrate specific for the insulin vis-a-vis the IGF-1 receptor tyrosine kinase, the pp120 signaling pathway may constitute a novel mechanism for the distinct cellular effects of insulin and IGF-1, the former being principally involved in metabolism, and the latter in mitogenesis.

Original languageEnglish (US)
Pages (from-to)6827-6834
Number of pages8
JournalBiochemistry
Volume36
Issue number22
DOIs
StatePublished - Jun 3 1997
Externally publishedYes

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Somatomedin Receptors
IGF Type 1 Receptor
Phosphorylation
Somatomedins
Insulin
Insulin Receptor
Protein-Tyrosine Kinases
Receptor Protein-Tyrosine Kinases
Substrates
Membrane Glycoproteins
Hepatocytes
Fibroblasts
Cell membranes
Cell Membrane
Metabolism
Ligands

ASJC Scopus subject areas

  • Biochemistry

Cite this

Differential phosphorylation of pp120 by insulin and insulin-like growth factor-I receptors : Role for the C-terminal domain of the β-subunit. / Najjar, Sonia M.; Blakesley, Vicky A.; Li Calzi, Sergio; Kato, Hisanori; LeRoith, Derek; Choice, Curtis.

In: Biochemistry, Vol. 36, No. 22, 03.06.1997, p. 6827-6834.

Research output: Contribution to journalArticle

Najjar, Sonia M. ; Blakesley, Vicky A. ; Li Calzi, Sergio ; Kato, Hisanori ; LeRoith, Derek ; Choice, Curtis. / Differential phosphorylation of pp120 by insulin and insulin-like growth factor-I receptors : Role for the C-terminal domain of the β-subunit. In: Biochemistry. 1997 ; Vol. 36, No. 22. pp. 6827-6834.
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