Surfing the insulin signaling web

Obberghen, E. Van; Baron, Véronique; Delahaye, Laurent; Emanuelli, Brice; Filippa, Nathalie; Giorgetti‐Peraldi, Sophie; Lebrun, Patricia; Mothe-Satney, Isabelle; Peraldi, Pascal; Rocchi, Stéphane; Sawka‐Verhelle, Dominique; Tartare‐Deckert, Sophie; Giudicelli, J.

doi:10.1046/j.1365-2362.2001.00896.x

Cited by 82 publications

(64 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, the Grb7/Grb10/Grb14 family of adapter proteins, in addition to their SH2 domains, contain novel receptor-specific interaction domains (BPS) that allow them to interact differentially with receptors (61,62). Moreover, a domain in IRS-2, the kinase regulatory loop-binding (KRLB) domain, interacts specifically with the insulin receptor but not the highly related IGF-1 receptor (63). Intriguingly, MBD, BPS, and KRLB all bind to kinase domains, and all three interactions require receptor kinase activity (61,64).…”

Section: A Peptide Motif Within the Gab1 Mbd Is Sufficient To Interacmentioning

confidence: 99%

Grb2-independent Recruitment of Gab1 Requires the C-terminal Lobe and Structural Integrity of the Met Receptor Kinase Domain

Lock

Frigault

Saucier

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

The Gab1 docking protein forms a platform for the assembly of a multiprotein signaling complex downstream from receptor tyrosine kinases. In general, recruitment of Gab1 occurs indirectly, via the adapter protein Grb2. In addition, Gab1 interacts with the Met/ hepatocyte growth factor receptor in a Grb2-independent manner. This interaction requires a Met binding domain (MBD) in Gab1 and is essential for Met-mediated epithelial morphogenesis. The Gab1 MBD has been proposed to act as a phosphotyrosine binding domain that binds Tyr-1349 in the Met receptor. We show that a 16-amino acid motif within the Gab1 MBD is sufficient for interaction with the Met receptor, suggesting that it is unlikely that the Gab1 MBD forms a structured domain. Alternatively, the structural integrity of the Met receptor, and residues upstream of Tyr-1349 located in the C-terminal lobe of the kinase domain, are required for Grb2-independent interaction with the Gab1 MBD. Moreover, the substitution of Tyr-1349 with an acidic residue allows for the recruitment of the Gab1 MBD and for phosphorylation of Gab1. We propose that Gab1 and the Met receptor interact in a novel manner, such that the activated kinase domain of Met and the negative charge of phosphotyrosine 1349 engage the Gab1 MBD as an extended peptide ligand.

show abstract

Section: A Peptide Motif Within the Gab1 Mbd Is Sufficient To Interacmentioning

confidence: 99%

Grb2-independent Recruitment of Gab1 Requires the C-terminal Lobe and Structural Integrity of the Met Receptor Kinase Domain

Lock

Frigault

Saucier

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…3,[6][7][8] The structure of Dok-1 presents some similarities with other adapter molecules such as Gab proteins or insulin receptor substrate (IRS) proteins. 9,10 Two proteins sharing extensive sequence homology with the amino-terminal part (PH and PTB domains) of Dok-1 have been cloned: Dok-2 (also known as FRIP or Dok-R) [11][12][13][14] and Dok-3 (also known as Dok-L). 15,16 These proteins are essentially expressed in hematopoietic tissues.…”

Section: Introductionmentioning

confidence: 99%

DOK4 and DOK5: new dok-related genes expressed in human T cells

et al. 2003

View full text Add to dashboard Cite

Dok proteins are adapter proteins involved in signal transduction. Several intracellular proteins expressed in lymphocytes meet the criteria of membrane-associated adapter proteins such as members of the Dok family. To understand the role and the formation of multiprotein networks involving Dok proteins in T lymphocytes, we search for potential additional members of this family. Here, we describe the two new human dok-related genes DOK4 and DOK5 and present data showing the expression of DOK4 and DOK5 genes in T cells. These genes are the orthologues of mouse Dok4 and Dok5 genes. Based on analysis of phylogenetic trees and exon/intron structure of Dok family members, DOK4 and DOK5 define a subfamily within dok genes distinct from DOK1, DOK2 and DOK3. So, Dok-4 and Dok-5 molecules constitute a new group of adapter proteins in T cells, requiring further functional analysis.

show abstract

“…Following insulin binding to its receptor, the receptor tyrosine kinase is activated, leading to the phosphorylation of several intracellular protein substrates. These rapid events generate multiple signaling cascades that eventuate in the final cellular responses to insulin (1,2). Insulin-activated signaling modules include the Ras/mitogen-activated protein kinase, the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (PKB) and the protein kinase C (PKC) pathways (3,4).…”

mentioning

confidence: 99%

Methylglyoxal Impairs the Insulin Signaling Pathways Independently of the Formation of Intracellular Reactive Oxygen Species

et al. 2006

View full text Add to dashboard Cite

Nonenzymatic glycation is increased in diabetes and leads to elevated levels of advanced glycation end products (AGEs), which link hyperglycemia to the induction of insulin resistance. In hyperglycemic conditions, intracellularly formed ␣-ketoaldehydes, such as methylglyoxal, are an essential source of intracellular AGEs, and the abnormal accumulation of methylglyoxal is related to the development of diabetes complications in various tissues and organs. We have previously shown in skeletal muscle that AGEs induce insulin resistance at the level of metabolic responses. Therefore, it was important to extend our work to intermediates of the biosynthetic pathway leading to AGEs. Hence, we asked the question whether the reactive ␣-ketoaldehyde methylglyoxal has deleterious effects on insulin action similar to AGEs. We analyzed the impact of methylglyoxal on insulin-induced signaling in L6 muscle cells. We demonstrate that a short exposure to methylglyoxal induces an inhibition of insulin-stimulated phosphorylation of protein kinase B and extracellular-regulated kinase 1/2, without affecting insulin receptor tyrosine phosphorylation. Importantly, these deleterious effects of methylglyoxal are independent of reactive oxygen species produced by methylglyoxal but appear to be the direct consequence of an impairment of insulin-induced insulin receptor substrate-1 tyrosine phosphorylation subsequent to the binding of methylglyoxal to these proteins. Our data suggest that an increase in intracellular methylglyoxal content hampers a key molecule, thereby leading to inhibition of insulin-induced signaling. By such a mechanism, methylglyoxal may not only induce the debilitating complications of diabetes but may also contribute to the pathophysiology of diabetes in general.

show abstract

Surfing the insulin signaling web

Cited by 82 publications

References 92 publications

Grb2-independent Recruitment of Gab1 Requires the C-terminal Lobe and Structural Integrity of the Met Receptor Kinase Domain

Grb2-independent Recruitment of Gab1 Requires the C-terminal Lobe and Structural Integrity of the Met Receptor Kinase Domain

DOK4 and DOK5: new dok-related genes expressed in human T cells

Methylglyoxal Impairs the Insulin Signaling Pathways Independently of the Formation of Intracellular Reactive Oxygen Species

Contact Info

Product

Resources

About