Epidermal Growth Factor and Membrane Trafficking

Barbieri, M. Alejandro; Roberts, Richard L.; Gumusboga, Aysel; Highfield, Hilary A.; Álvarez-Domínguez, Carmen; Wells, Alan; Stahl, Philip D.

doi:10.1083/jcb.151.3.539

Cited by 218 publications

(118 citation statements)

References 62 publications

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“…Agonist activation of the epidermal growth factor receptor (EGFR) also results in the recruitment of intracellular proteins involved in endocytic trafficking. In particular, EGFR stimulation leads to the activation and plasma membrane translocation of Rab5a (32). However, unlike what we observe for the AT 1A R, EGFR internalization is blocked by Rab5a-S34N.…”

Section: Rab5 Association With the Angiotensin II Type 1a Receptorcontrasting

confidence: 54%

“…However, unlike what we observe for the AT 1A R, EGFR internalization is blocked by Rab5a-S34N. Furthermore, EGFR-dependent Rab5a activation requires the stimulation of a tyrosine kinase signal transduction cascade that leads to the activation of uncharacterized intermediary Rab5a regulatory proteins (32). In contrast, the activation of Rab5a by the AT 1A R appears to involve the direct association of the receptor with the GTPase.…”

Section: Rab5 Association With the Angiotensin II Type 1a Receptorcontrasting

confidence: 48%

See 1 more Smart Citation

Rab5 Association with the Angiotensin II Type 1A Receptor Promotes Rab5 GTP Binding and Vesicular Fusion

Seachrist¹,

Laporte²,

Dale³

et al. 2002

Journal of Biological Chemistry

128

123

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Section: Rab5 Association With the Angiotensin II Type 1a Receptorcontrasting

confidence: 54%

Section: Rab5 Association With the Angiotensin II Type 1a Receptorcontrasting

confidence: 48%

Rab5 Association with the Angiotensin II Type 1A Receptor Promotes Rab5 GTP Binding and Vesicular Fusion

Seachrist¹,

Laporte²,

Dale³

et al. 2002

Journal of Biological Chemistry

128

123

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“…Rab 5 mediates fusion of vesicles to early endosomes (38,39). Trypanosome Rab 5A and Rab 5B localize to separate endosomal compartments and associate with distinct cargos (39).…”

Section: Evolution Of Early Endosomal Rabs (Rab 5)mentioning

confidence: 99%

Phylogeny of endocytic components yields insight into the process of nonendosymbiotic organelle evolution

Dacks

Poon

Field³

2008

Proc. Natl. Acad. Sci. U.S.A.

124

138

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The process by which some eukaryotic organelles, for example the endomembrane system, evolved without endosymbiotic input remains poorly understood. This problem largely arises because many major cellular systems predate the last common eukaryotic ancestor (LCEA) and thus do not provide examples of organellogenesis in progress. A model is emerging whereby gene duplication and divergence of multiple ''specificity-'' or ''identity-'' encoding proteins for the various endomembranous organelles produced the diversity of nonendosymbiotically derived cellular compartments present in modern eukaryotes. To address this possibility, we analyzed three molecular components of the endocytic membrane-trafficking machinery. Phylogenetic analyses of the endocytic syntaxins, Rab 5, and the ␤-adaptins each reveal a pattern of ancestral, undifferentiated endocytic homologues in the LCEA. Subsequently, these undifferentiated progenitors independently duplicated in widely divergent lineages, convergently producing components with similar endocytic roles, e.g., ␤1 and ␤2-adaptin. In contrast, ␤3, ␤4, and all other adaptin complex subunits, as well as paralogues of the syntaxins and Rabs specific for the other membrane-trafficking organelles, all evolved before the LCEA. Thus, the process giving rise to the differentiated organelles of the endocytic system appears to have been interrupted by the major speciation event that produced the extant eukaryotic lineages. These results suggest that although many endocytic components evolved before the LCEA, other major features evolved independently and convergently after diversification into the primary eukaryotic supergroups. This finding provides an example of a basic cellular system that was simpler in the LCEA than in many extant eukaryotes and yields insight into nonendosymbiotic organelle evolution.adaptin ͉ Rab ͉ SNARE ͉ trafficking ͉ autogenous

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“…However, down-regulation of all three Rab5 isoforms significantly decreased the internalization of both EGF and Tfn (32). Experiments utilizing dominant negative Rab5A suggest a requirement for Rab5 activity in both IR and EGF internalization (14,33).…”

mentioning

confidence: 99%

Insulin-stimulated Interaction between Insulin Receptor Substrate 1 and p85α and Activation of Protein Kinase B/Akt Require Rab5

Lodhi

Saltiel

et al. 2006

Journal of Biological Chemistry

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Binding of insulin to the insulin receptor initiates a cascade of protein phosphorylation and effector recruitment events leading to the activation of multiple distinct signaling pathways. Previous studies suggested that the diversity and specificity of insulin signal transduction are accomplished by both subcellular localization of receptor and the selective activation of downstream signaling molecules. The small GTPase Rab5 is a key regulator of endocytosis. Three Rab5 isoforms (Rab5a, -5b, and -5c) have been identified. Here we exploited the RNA interference technique to specifically knock down individual Rab5 isoforms to determine the cellular function of Rab5 in distinct insulin signaling pathways. Small interference RNA against a single Rab5 isoform had no effect on protein kinase B (PKB)/Akt or MAPK activation by insulin in NIH3T3 cells overexpressing human insulin receptor. However, simultaneous knockdown of all three Rab5 isoforms dramatically attenuated PKB/Akt activation by insulin without affecting MAPK activation. This inhibition of PKB/Akt activation was because of the impaired interaction between insulin receptor substrate 1 and the p85␣ subunit of phosphatidylinositol 3-kinase. These results indicate a requirement of Rab5 in presenting p85 to insulin receptor substrate 1. Additional evidence supporting a role for Rab5 was suggested by studies with GAPex-5, a vps9 domain containing exchange factor. Down-regulation of GAPex-5 impaired insulin-stimulated PKB/Akt activation. Collectively, this study indicates the involvement of Rab5 in insulin signaling.Both environmental and genetic factors contribute to the development of type 2 diabetes mellitus. Although detailed mechanisms underlying the development of this disorder remain unknown, impairment of insulin action has been clearly established as an early defect in the pathogenesis of type 2 diabetes (1, 2). Binding of insulin to the insulin receptor (IR) 2 causes receptor autophosphorylation and activation of its intrinsic kinase activity. Activated IR phosphorylates a variety of intracellular substrates, most notably the insulin receptor substrate (IRS) proteins (3, 4). Tyrosine phosphorylation of these proteins provides binding sites for downstream effectors with Src homolog 2 domains or phosphotyrosine binding domains that activate multiple signaling pathways required for insulin-stimulated glucose uptake and maintenance of energy homeostasis (5, 6). Type 1A phosphatidylinositol 3-kinase (PI3K) represents a primary target of insulin action (7). Phosphorylation of IRS1 and/or IRS2 on tyrosine residues by activated IR creates recognition sites for the p85 regulatory subunit of PI3K, thereby allowing the activation of the p110 catalytic subunit (8). PI3K-generated phosphoinositides PI(3,4,5)P 3 and PI(3,4)P 2 recruit protein kinase B (PKB)/Akt and 3-phosphoinositide-dependent kinase to the membrane, resulting in PKB/Akt phosphorylation and activation (9 -11). Recent studies also demonstrated a second requisite pathway that involves recruitment of ty...

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Epidermal Growth Factor and Membrane Trafficking

Cited by 218 publications

References 62 publications

Rab5 Association with the Angiotensin II Type 1A Receptor Promotes Rab5 GTP Binding and Vesicular Fusion

Rab5 Association with the Angiotensin II Type 1A Receptor Promotes Rab5 GTP Binding and Vesicular Fusion

Phylogeny of endocytic components yields insight into the process of nonendosymbiotic organelle evolution

Insulin-stimulated Interaction between Insulin Receptor Substrate 1 and p85α and Activation of Protein Kinase B/Akt Require Rab5

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