Insulin-like Growth Factor Type-I Receptor Internalization and Recycling Mediate the Sustained Phosphorylation of Akt

Romanelli, Robert J.; LeBeau, Andrew; Fulmer, Clifton G.; Lazzarino, Deborah A.; Hochberg, Alan M.; Wood, Teresa L.

doi:10.1074/jbc.m704309200

Cited by 111 publications

(93 citation statements)

References 49 publications

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“…Based on evidence for the involvement of GIPC in endocytic trafficking, Wu et al (2006) hypothesized that xGIPC promotes IGF-IR recycling and, consequently, is required for sustained signal transduction and Xenopus eye development. This hypothesis is consistent with our demonstration of sustained PI3-K/Akt signaling in glial progenitors through IGF-IR recycling (Romanelli et al 2007). Although gaps remain in understanding precisely how GIPC regulates RTKs, this receptor-interacting protein has emerged as an interesting target for investigation of RTK trafficking, the regulation of signal transduction and resultant cellular responses.…”

Section: Receptor Interacting Proteinssupporting

confidence: 74%

“…Moreover, Akt co-localizes with Trk within intracellular membrane fractions in a brain-derived neurotrophic factor (BDNF)-dependent manner in primary neurons (Yano and Chao 2005). Recently, we also demonstrated that IGF-I stimulated Akt phosphorylation requires IGF-IR internalization in glial progenitors (Romanelli et al 2007). These data strongly suggest that endosome-bound receptors are competent for signaling in various cell types and that internalization, in some cases, is required for activated receptors to interact with the appropriate signaling complexes.…”

Section: Rtk Signaling: Plasma Membrane Versus Endosomementioning

confidence: 92%

“…2b). Interestingly, the ability of IGF-I to promote sustained Akt phosphorylation in these cells requires the internalization and recycling of the IGF-IR (Romanelli et al 2007) (Fig. 3).…”

Section: Degradation Versus Recyclingmentioning

confidence: 99%

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Directing traffic in neural cells: determinants of receptor tyrosine kinase localization and cellular responses

Romanelli

Wood²

2008

Journal of Neurochemistry

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The trafficking of receptor tyrosine kinases (RTKs) to distinct subcellular locations is essential for the specificity and fidelity of signal transduction and biological responses. This is particularly important in the PNS and CNS in which RTKs mediate key events in the development and maintenance of neurons and glia through a wide range of neural processes, including survival, proliferation, differentiation, neurite outgrowth, and synaptogenesis. The mechanisms that regulate the targeting of RTKs to their subcellular destinations for appropriate signal transduction, however, are still elusive. In this review, we discuss evidence for the spatial organization of signaling machinery into distinct subcellular compartments, as well as the role for ligand specificity, receptor sorting signals, and lipid raft microdomains in RTK targeting and the resultant cellular responses in neural cells.

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Section: Receptor Interacting Proteinssupporting

confidence: 74%

Section: Rtk Signaling: Plasma Membrane Versus Endosomementioning

confidence: 92%

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Directing traffic in neural cells: determinants of receptor tyrosine kinase localization and cellular responses

Romanelli

Wood²

2008

Journal of Neurochemistry

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“…Tyrosine kinase receptors are internalized and degraded on growth factor stimulation. 38,39 Thus, IGF1R protein levels are affected by receptor activation and turnover and do not always reflect receptor expression levels. In addition, immunohistochemistry results can be influenced by a variety of technical factors, including tissue storage and fixation conditions, antigen retrieval protocols, antibody specificity, antibody detection systems, and other methodologic factors.…”

Section: Discussionmentioning

confidence: 99%

Expression of the IGF Axis Is Decreased in Local Prostate Cancer but Enhanced after Benign Prostate Epithelial Differentiation and TGF-β Treatment

Massoner¹,

Rennau²,

Heidegger³

et al. 2011

The American Journal of Pathology

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The insulin-like growth factor (IGF) axis is a molecular pathway intensively investigated in cancer research. Clinical trials targeting the IGF1 receptor (IGF1R) in different tumors, including prostate cancer, are under way. Although studies on the IGF axis in prostate cancer have already entered into clinical trials, the expression and functional role of the IGF axis in benign prostate and in prostate cancer needs to be better defined. We determined mRNA expression levels of the IGF axis in microdissected tissue specimens of local prostate cancer using quantitative PCR. All members of the IGF axis, including IGF1, IGF2, IGF binding proteins 1 through 6, and insulin receptor, were measured in both the stromal and epithelial compartments of the prostate. IGF1, IGF2, IGF1R, and insulin receptor were down-regulated in local prostate cancer tissue compared with matched benign tissue, suggesting that the IGF axis is not induced during prostate cancer development. Using a new prostate epithelial differentiation model, we demonstrate that the expression of the IGF axis is enhanced during normal prostate epithelial differentiation and regulated by tumor growth factor (TGF)-␤. Our data reveal a functional role of the IGF axis in prostate differentiation, underscoring the importance of the IGF axis in normal development and emphasizing the importance of accurate target validation before moving to advanced clinical trials.

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“…Mislocalization of IRS-1 reduced IGF-I-dependent tyrosine phosphorylation of IRS-1 and the association with PI 3-kinase without affecting phosphorylation of IGF-IR. Several reports suggest that internalization of IR/IGF-IR is required for proper signal transduction (44)(45)(46)(47). These observations raise the possibility that the IRS-1-IGF-IR association should be spatially restricted in the intracellular membrane compartment, and therefore a defect in AP-1 transport to such compartment could result in reduced tyrosine phosphorylation of IRS-1 by IGF-IR.…”

Section: Discussionmentioning

confidence: 99%

The AP-1 Complex Regulates Intracellular Localization of Insulin Receptor Substrate 1, Which Is Required for Insulin-Like Growth Factor I-Dependent Cell Proliferation

Yoneyama

Matsuo

Take

et al. 2013

Molecular and Cellular Biology

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The activation of the insulin/insulin-like growth factor I (IGF-I) receptor and the subsequent tyrosine phosphorylation of insulin receptor substrates (IRSs) are key initial events in a variety of insulin/IGF bioactivities, including mitogenesis. It has been reported that IRS-1 associates with intracellular membrane compartments, and this localization is believed to be important for insulin/IGF signal transduction. However, the molecular mechanisms underlying IRS-1 localization remain unclear. Here we show that in L6 myoblasts, IRS-1 associates with 1A of the ubiquitously expressed AP-1 complex, which packages cargo proteins into clathrin-coated vesicles derived from intracellular membranes. While wild-type IRS-1 was predominantly localized to vesicular structures, IRS-1 mutants lacking three YXX⌽ motifs responsible for binding to 1A were mislocalized to the mannose-6-phosphate receptor-positive structures, suggesting that AP-1-dependent transport to peripheral vesicles is inhibited in these mutants. Furthermore, deletion of AP-1 binding sites in IRS-1 impaired IGF-I-induced cell proliferation, accompanied by reduced tyrosine phosphorylation of IRS-1 and its association with phosphoinositide (PI) 3-kinase. These data demonstrate the importance of AP-1-dependent localization of IRS-1 in mediating IGF-I-stimulated signaling and maximum mitogenic response.

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Insulin-like Growth Factor Type-I Receptor Internalization and Recycling Mediate the Sustained Phosphorylation of Akt

Cited by 111 publications

References 49 publications

Directing traffic in neural cells: determinants of receptor tyrosine kinase localization and cellular responses

Directing traffic in neural cells: determinants of receptor tyrosine kinase localization and cellular responses

Expression of the IGF Axis Is Decreased in Local Prostate Cancer but Enhanced after Benign Prostate Epithelial Differentiation and TGF-β Treatment

The AP-1 Complex Regulates Intracellular Localization of Insulin Receptor Substrate 1, Which Is Required for Insulin-Like Growth Factor I-Dependent Cell Proliferation

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