Differential Phosphorylation of pp120 by Insulin and Insulin-like Growth Factor-1 Receptors:  Role for the C-Terminal Domain of the β-Subunit

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

doi:10.1021/bi962634h

Cited by 34 publications

(32 citation statements)

References 40 publications

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“…The first steps in the signaling networks downstream of the insulin receptor and IGF-IR are similar, although not identical (38). Both ligands have major influences on protein translation via pathways linking receptor activation to AKT and mTOR, and they also influence transcriptional programs.…”

Section: The Insulin/igf Receptor Familymentioning

confidence: 99%

The Insulin Receptor/Insulin-Like Growth Factor Receptor Family as a Therapeutic Target in Oncology

Pollak

2012

Clinical Cancer Research

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Over the past decade, encouraging preclinical and early clinical data concerning the relevance of the insulin receptor/insulin-like growth factor (IGF) receptor family to neoplasia led to ambitious clinical trial programs of more than a dozen drug candidates that target these receptors. These candidates include antireceptor antibodies, antiligand antibodies, receptor-specific tyrosine kinase inhibitors, and agents such as picropodophyllin and metformin that have novel mechanisms of action. Several recently reported phase III clinical trials of anti-IGF-I receptor antibodies have been disappointing and are sufficient to disprove the hypothesis that the antibodies tested have large favorable impacts on unselected patients with cancer. However, many of these trials were designed prior to recent insights concerning pathophysiology and predictive biomarkers. Future studies are required, but it will be important to optimize their design rather than simply repeat the approaches taken to date.

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Section: The Insulin/igf Receptor Familymentioning

confidence: 99%

The Insulin Receptor/Insulin-Like Growth Factor Receptor Family as a Therapeutic Target in Oncology

Pollak

2012

Clinical Cancer Research

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“…Najjar and coworkers identified pp120, a plasma membrane glycoprotein, as a specific substrate for the IR but not the IGF-IR (Najjar et al, 1997;Soni et al, 2000). Phosphorylation of pp120 is required for its function in insulin endocytosis (Formisano et al, 1995), and also for its inhibitory effect on the mitogenic actions of insulin (Soni et al, 2000).…”

Section: Receptor Functioningmentioning

confidence: 99%

The Insulin‐Like Growth Factor System

Roith

2003

Journal of Diabetes Research

165

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The insulin-like growth factor (IGF) system in ubiquitous and plays a role in every tissue of the body. It is comprised of ligands, receptors and binding proteins, each with specific functions. While it plays an essential role in embryonic and post-natal development, the IGF system is also important in normal adult physiology. There are now numerous examples of diseases such as diabetes, cancer, and malnutrition in which the IGF system is a major player and, not surprisingly, there are attempts to affect these disorders by manipulating the system.

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“…Najjar and coworkers identified pp120, a plasma membrane glycoprotein, which is a substrate for the IR but not for the IGF-1R (Najjar et al, 1997;Soni et al, 2000). Phosphorylation of pp120 is required for its function in insulin endocytosis (Formisano et al, 1995), bile acid transport (Sippel et al, 1994), tumor suppression (Kleinerman et al, 1995), and its inhibitory effect on the mitogenic actions of insulin (Soni et al, 2000).…”

Section: Proximal Substratesmentioning

confidence: 99%

Microarray Analysis and Identification of Novel Molecules Involved in Insulin-like Growth Factor-1 Receptor Signaling and Gene Expression

Dupont

Se²,

Jc³

et al. 2003

Recent Progress in Hormone Research

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The insulin receptor (IR) and the insulin-like growth factor-1 receptor (IGF-1R) are members of the same subfamily of receptor tyrosine kinases. The two receptors phosphorylate many of the same substrates and activate the same signaling modules, including the mitogen-activated protein kinase (MAPK) and phosphatidyl inositol 3Ј kinase (PI3K) signaling pathways. Although the IR and IGF-1R share some redundant functions in metabolism, cell growth, differentiation, and apoptosis, they also exhibit distinct physiological roles. Some of these may be due to differences in tissue distribution, receptor structure, formation of hybrid receptors, or mechanisms of ligand binding. However, the divergent effects of insulin and IGF-1 also may be explained by specificity in the intracellular signals generated by insulin and IGF-1. In particular, the IR and IGF-1R are capable of triggering their own biological responses by using specific or preferential substrates, molecular adapters, or signaling pathways. In a recent study, we used cDNA microarray analysis to identify genes differentially regulated by insulin and IGF-1. Mouse NIH-3T3 fibroblasts expressing either the wild-type human IGF-1R or IR were stimulated with either IGF-1 or insulin, respectively. We identified 39 genes differentially regulated by insulin and IGF-1. Most of these genes had not been reported previously to be responsive to insulin or IGF-1. The genes induced by IGF-1 generally were involved in mitogenesis or differentiation, while the genes found to be induced by insulin did not conform to any particular category. In a separate study, immortalized breast epithelial cells were stimulated with IGF-1 and a cDNA microarray analysis was used to generate a profile of IGF-1-regulated genes. A number of genes known to be involved in angiogenesis were found to be regulated by IGF-1. These results strongly suggest that this technology may be extremely useful in identifying groups of genes that are specifically regulated by different ligands and their activated receptors.

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Differential Phosphorylation of pp120 by Insulin and Insulin-like Growth Factor-1 Receptors: Role for the C-Terminal Domain of the β-Subunit

Cited by 34 publications

References 40 publications

The Insulin Receptor/Insulin-Like Growth Factor Receptor Family as a Therapeutic Target in Oncology

The Insulin Receptor/Insulin-Like Growth Factor Receptor Family as a Therapeutic Target in Oncology

The Insulin‐Like Growth Factor System

Microarray Analysis and Identification of Novel Molecules Involved in Insulin-like Growth Factor-1 Receptor Signaling and Gene Expression

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