Research Topics
Genomes and Genes
| Alexander SorkinSummaryAffiliation: University of Colorado Health Sciences Center Country: USA Publications
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Detail Information
Publications
Lysosomal targeting of epidermal growth factor receptors via a kinase-dependent pathway is mediated by the receptor carboxyl-terminal residues 1022-1123E Kornilova
Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
J Biol Chem 271:30340-6. 1996..These results support the view that the receptor kinase activity is important for ligand-induced sorting of EGF receptors to the pathway of lysosomal degradation...
Coordinated traffic of Grb2 and Ras during epidermal growth factor receptor endocytosis visualized in living cellsXuejun Jiang
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80111, USA
Mol Biol Cell 13:1522-35. 2002..These data point to the potential for endosomes to serve as sites of generation for persistent signaling through Ras...- Growth factor receptor binding protein 2-mediated recruitment of the RING domain of Cbl to the epidermal growth factor receptor is essential and sufficient to support receptor endocytosisFangtian Huang
Department of Pharmacology, University of Colorado Health Sciences Center, Aurora, CO 80045, USA
Mol Biol Cell 16:1268-81. 2005..We concluded that Grb2-mediated recruitment of the functional RING domain of Cbl to the EGFR is essential and sufficient to support receptor endocytosis... - TRKing signals through the GolgiAlexander Sorkin
Department of Pharmacology, University of Colorado Health Sciences Center, Aurora, Colorado 80045 3649, USA
Sci STKE 2005:pe1. 2005.... - Ubiquitination without E3Alexander Sorkin
Department of Pharmacology, University of Colorado Health Sciences Center, Aurora, CO 80045, USA
Mol Cell 26:771-3. 2007..In the current issue of Molecular Cell, Hoeller et al. (2007) demonstrated that proteins bearing ubiquitin-binding domains (UBDs) can be ubiquitinated directly by E2-conjugating enzymes, bypassing the requirement for E3 ubiquitin ligases... - Endocytosis and intracellular trafficking of ErbBsAlexander Sorkin
Department of Pharmacology, University of Colorado Denver Anschutz Medical Center, Aurora, Colorado 80045 0508, USA
Exp Cell Res 314:3093-106. 2008..However, these ErbBs are internalized and targeted to lysosomes less efficiently than EGFR. When overexpressed endocytosis-impaired ErbBs may inhibit the internalization and degradation of EGFR... - Endocytosis and intracellular trafficking of ErbBsAlexander Sorkin
Department of Pharmacology, University of Colorado Denver Anschutz Medical Center, Aurora, Colorado 80045 0508, USA
Exp Cell Res 315:683-96. 2009..However, these ErbBs are internalized and targeted to lysosomes less efficiently than EGFR. When overexpressed endocytosis-impaired ErbBs may inhibit the internalization and degradation of EGFR... - Cargo recognition during clathrin-mediated endocytosis: a team effortAlexander Sorkin
Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
Curr Opin Cell Biol 16:392-9. 2004..These alternative mechanisms appear to be particularly important during clathrin-mediated endocytosis of signaling receptors... - Signal transduction and endocytosis: close encounters of many kindsAlexander Sorkin
Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80111, USA
Nat Rev Mol Cell Biol 3:600-14. 2002..Recent studies of protein tyrosine kinases and G-protein-coupled receptors have shed new light on the mechanisms and functional consequences of this bidirectional interplay between signalling and membrane-transport networks... - Endocytosis and intracellular sorting of receptor tyrosine kinasesA Alexander
Department of Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262, USA
Front Biosci 3:d729-38. 1998.... - Interaction of EGF receptor and grb2 in living cells visualized by fluorescence resonance energy transfer (FRET) microscopyA Sorkin
Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80111, USA
Curr Biol 10:1395-8. 2000..The work also highlights the potential of FRET microscopy in the study of subcellular compartmentalization of protein-protein interactions in living cells... - Internalization of the epidermal growth factor receptor: role in signallingA Sorkin
Department of Pharmacology, University of Colorado Health Science Center, 4200 E Ninth Avenue, Denver, CO 80111, USA
Biochem Soc Trans 29:480-4. 2001..Moreover, in contrast with previous biochemical studies, FRET experiments show that a large pool of Grb2 and Shc is associated with EGFRs for a prolonged period after EGF stimulation... - Enhanced ubiquitylation and accelerated degradation of the dopamine transporter mediated by protein kinase CManuel Miranda
Department of Pharmacology, University of Colorado Health Sciences Center, Aurora, Colorado 80045, USA
J Biol Chem 280:35617-24. 2005..Altogether, these data suggest that PKC-induced DAT ubiquitylation may target DAT to lysosomal degradation... - Multiple mechanisms collectively regulate clathrin-mediated endocytosis of the epidermal growth factor receptorLai Kuan Goh
Department of Pharmacology, School of Medicine, University of Colorado Denver, Aurora, CO 80045, USA
J Cell Biol 189:871-83. 2010..Analysis of the signaling kinetics of this mutant revealed that EGFR internalization is required for the sustained activation of protein kinase B/AKT but not for the activation of mitogen-activated protein kinase... - Tyrosine phosphorylation of the beta2 subunit of clathrin adaptor complex AP-2 reveals the role of a di-leucine motif in the epidermal growth factor receptor traffickingFangtian Huang
Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
J Biol Chem 278:43411-7. 2003..Surprisingly, mutation of the Leu-1010/Leu-1011 motif resulted in impaired degradation of EGF receptors, suggesting the role of this motif in lysosomal targeting of the receptor... - Multiple molecular determinants in the carboxyl terminus regulate dopamine transporter export from endoplasmic reticulumManuel Miranda
Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
J Biol Chem 279:30760-70. 2004.... - Recruitment of Uev1B to Hrs-containing endosomes and its effect on endosomal traffickingJason E Duex
Department of Pharmacology, University of Colorado Denver Medical School, Aurora, Colorado, USA
Exp Cell Res 316:2136-51. 2010..Together, the data show that elevated levels of Uev1B protein in cells lead to decreased efficiency of endosomal sorting by associating with ubiquitinated proteins and Hrs... - Constitutive and protein kinase C-induced internalization of the dopamine transporter is mediated by a clathrin-dependent mechanismTatiana Sorkina
Department of Pharmacology, University of Colorado Health Sciences Center, Aurora, Colorado 80045, USA
Traffic 6:157-70. 2005..Altogether, the data suggest that both constitutive and protein kinase C-mediated internalization of DAT utilize the clathrin-dependent endocytic pathway, but likely involve unconventional mechanisms... - Endosomal targeting of MEK2 requires RAF, MEK kinase activity and clathrin-dependent endocytosisEmilia Galperin
Department of Pharmacology, University of Colorado at Denver and Health Sciences Center, Aurora, CO 80045, USA
Traffic 9:1776-90. 2008..We propose that the recruitment of MEK2 to endosomes can be a part of the negative feedback regulation of the EGFR-MAPK signaling pathway by endocytosis... - EGF receptor ubiquitination is not necessary for its internalizationFangtian Huang
Department of Pharmacology, University of Colorado Health Sciences Center, Aurora, CO 80045, USA
Proc Natl Acad Sci U S A 104:16904-9. 2007..Altogether these data emphasize the robustness of the EGFR internalization process, which can be controlled by multiple kinase- and ubiquitination-dependent and -independent mechanisms... - Three ubiquitin conjugation sites in the amino terminus of the dopamine transporter mediate protein kinase C-dependent endocytosis of the transporterManuel Miranda
Department of Pharmacology, University of Colorado Health Sciences Center, Aurora, CO 80045, USA
Mol Biol Cell 18:313-23. 2007..These data provide the first evidence that the ubiquitin moieties conjugated to DAT may serve as a molecular interface of the transporter interaction with the endocytic machinery... - Visualization of Rab5 activity in living cells by FRET microscopy and influence of plasma-membrane-targeted Rab5 on clathrin-dependent endocytosisEmilia Galperin
Department of Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262, USA
J Cell Sci 116:4799-810. 2003.... - Differential regulation of EGF receptor internalization and degradation by multiubiquitination within the kinase domainFangtian Huang
Department of Pharmacology, University of Colorado Health Sciences Center, Aurora, 80045, USA
Mol Cell 21:737-48. 2006..Taken together, these data provide direct evidence for the role of EGFR ubiquitination in receptor targeting to the lysosome and implicate Lys63-linked polyubiquitin chains in this sorting process... - Oligomerization of dopamine transporters visualized in living cells by fluorescence resonance energy transfer microscopyTatiana Sorkina
Department of Pharmacology and Neuroscience Program, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
J Biol Chem 278:28274-83. 2003..These data suggest that DAT oligomers are formed in the ER and then are constitutively maintained both at the cell surface and during trafficking between the plasma membrane and endosomes... - RNA interference screen reveals an essential role of Nedd4-2 in dopamine transporter ubiquitination and endocytosisTatiana Sorkina
Department of Pharmacology, University of Colorado at Denver and Health Sciences Center, Aurora, Colorado 80045, USA
J Neurosci 26:8195-205. 2006..A new mechanistic model of DAT endocytosis is proposed whereby the PKC-induced ubiquitination of DAT mediated by Nedd4-2 leads to interaction of DAT with adaptor proteins in coated pits and acceleration of DAT endocytosis... - Grb2 regulates internalization of EGF receptors through clathrin-coated pitsXuejun Jiang
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80111, USA
Mol Biol Cell 14:858-70. 2003..The data are consistent with the model whereby Grb2 participates in EGFR internalization through the recruitment of Cbl to the receptor, thus allowing proper ubiquitylation of EGFR and/or associated proteins at the plasma membrane... - Lysine 63-linked polyubiquitination of the dopamine transporter requires WW3 and WW4 domains of Nedd4-2 and UBE2D ubiquitin-conjugating enzymesArnau Vina-Vilaseca
Department of Pharmacology, University of Colorado Denver School of Medicine, Aurora, Colorado 80010, USA
J Biol Chem 285:7645-56. 2010..The model is proposed whereby each ubiquitinated DAT molecule is modified by a single four-ubiquitin Lys(63)-linked chain that can be conjugated to various lysine residues of DAT... - Analysis of clathrin-mediated endocytosis of epidermal growth factor receptor by RNA interferenceFangtian Huang
Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80111, USA
J Biol Chem 279:16657-61. 2004..This study demonstrates that the efficient gene silencing by rationally designed small interfering RNA can be used as an approach to functionally analyze the entire cellular machineries, such as the clathrin-coated pits and vesicles... - Epidermal growth factor receptor internalization through clathrin-coated pits requires Cbl RING finger and proline-rich domains but not receptor polyubiquitylationXuejun Jiang
Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80111, USA
Traffic 4:529-43. 2003..We propose that the RING domain of Cbl facilitates endocytosis either by epidermal growth factor receptor monoubiquitylation or by ubiquitylation of proteins associated with the receptor... - Differential subcellular distribution of endosomal compartments and the dopamine transporter in dopaminergic neuronsAnjali Rao
Department of Pharmacology, Anschutz Medical Center, University of Colorado Denver, Aurora, CO 80010, USA
Mol Cell Neurosci 46:148-58. 2011..Altogether, our data suggest that axonal DAT mainly shuttles between the plasma membrane and recycling endosomes, whereas in the somatodendritic region of neurons DAT traffics through all conventional endosomal pathways... - Quantitative analysis of endocytosis and turnover of epidermal growth factor (EGF) and EGF receptorAlexander Sorkin
Department of Pharmacology, University of Colorado Denver Medical School, Aurora, Colorado, USA
Curr Protoc Cell Biol . 2010.... - Effect of tyrosine kinase inhibitors on clathrin-coated pit recruitment and internalization of epidermal growth factor receptorTatiana Sorkina
Department of Pharmacology, University of Colorado Health Sciences Center, 4200 E Ninth Avenue, Denver, CO 80111, USA
J Biol Chem 277:27433-41. 2002..These data demonstrate that the activation of receptor kinase is essential for the initial, coated pit recruitment step of endocytosis... - Negative regulation of dopamine transporter endocytosis by membrane-proximal N-terminal residuesTatiana Sorkina
Department of Pharmacology and Neuroscience Program, Anschutz Medical Center, University of Colorado Denver, Aurora, Colorado 80045, USA
J Neurosci 29:1361-74. 2009..Thus, our studies reveal a new link between DAT endocytosis and conformation-dependent uptake activity that represents a novel mode for regulating DAT function... - Protein kinase C-dependent ubiquitination and clathrin-mediated endocytosis of the cationic amino acid transporter CAT-1Arnau Vina-Vilaseca
Department of Pharmacology, Anschutz Medical Center, University of Colorado Denver, Aurora, Colorado 80010, USA
J Biol Chem 286:8697-706. 2011..Altogether, our data suggest that ubiquitination mediated by NEDD4-2 or NEDD4-1 leading to clathrin-mediated endocytosis is the common mode of regulation of various transporter proteins by PKC... - Conversion of the monomeric red fluorescent protein into a photoactivatable probeVladislav V Verkhusha
Department of Pharmacology, University of Colorado Health Sciences Center, Aurora, CO 80045, USA
Chem Biol 12:279-85. 2005..PA-mRFP1s were used as protein tags to study the intracellular dynamics of GTPase Rab5... - Cyclin-dependent kinase 5 inhibitors: inhibition of dopamine transporter activityDavid A Price
Department of Pharmacology, University of Colorado Denver, Mail Stop 8303, RC1 North Tower, P18 6402K, 12800 East 19th Ave, Aurora, CO 80045, USA
Mol Pharmacol 76:812-23. 2009..Our study is the first to demonstrate that Cdk5 inhibitors reduce brain DAT activity via a mechanism that is independent of DAT trafficking and reverse-transport... - Three-chromophore FRET microscopy to analyze multiprotein interactions in living cellsEmilia Galperin
Department of Pharmacology, University of Colorado Health Sciences Center, Aurora, Colorado 80045, USA
Nat Methods 1:209-17. 2004..These data highlight the potential of 3-FRET microscopy in studies of spatial and temporal regulation of signaling processes in living cells... - RNA interference screen identifies Usp18 as a regulator of epidermal growth factor receptor synthesisJason E Duex
Department of Pharmacology, University of Colorado Denver, Aurora, CO 80045, USA
Mol Biol Cell 20:1833-44. 2009..Together, our data provide evidence for the novel mechanism of EGFR regulation at the translational step of receptor synthesis... - Rapid regulation of the dopamine transporter: role in stimulant addiction?Nancy R Zahniser
Department of Pharmacology, Neuroscience Program, University of Colorado Health Sciences Center at Fitzsimons, Aurora, CO 80045 0508, USA
Neuropharmacology 47:80-91. 2004..Future studies are needed to confirm these observations in neurons, as well as to elucidate the mechanisms of rapid DAT endocytic trafficking at neuronal synapses... - Regulation of receptors and transporters by ubiquitination: new insights into surprisingly similar mechanismsManuel Miranda
Department of Pharmacology, University of Colorado Health Sciences Center, Aurora, CO 80045, USA
Mol Interv 7:157-67. 2007..How ubiquitination controls the endocytosis and turnover of these proteins will be also discussed... - Endocytosis and signalling: intertwining molecular networksAlexander Sorkin
Department of Pharmacology, University of Colorado Denver School of Medicine, Aurora, 80010, USA
Nat Rev Mol Cell Biol 10:609-22. 2009..The mechanistic and functional principles that underlie the relationship between signalling and endocytosis in cell biology are becoming increasingly evident across many systems... - Trafficking of dopamine transporters in psychostimulant actionsNancy R Zahniser
Department of Pharmacology, University of Colorado Denver, Aurora, CO 80045, USA
Semin Cell Dev Biol 20:411-7. 2009..Recent reports have begun to elucidate the molecular mechanisms of these psychostimulant effects and link changes in DAT trafficking to psychostimulant-induced reward/reinforcement in animal models... - Visualization of Rab5 activity in living cells using FRET microscopyEmilia Galperin
Methods Enzymol 403:119-34. 2005..l). The results of the 3-FRET analysis suggest that GTP-bound Rab5 is capable of oligomerization and present in multiprotein complexes... - Direct interaction of Cbl with pTyr 1045 of the EGF receptor (EGFR) is required to sort the EGFR to lysosomes for degradationLene Melsaether Grøvdal
Institute of Pathology, University of Oslo, Rikshospitalet, N 0027 Oslo, Norway
Exp Cell Res 300:388-95. 2004.... - Protein kinaseCdelta-calmodulin crosstalk regulates epidermal growth factor receptor exit from early endosomesAnna Lladó
Departament de Biologia Cellular, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain
Mol Biol Cell 15:4877-91. 2004..These results demonstrate a specific interplay between calmodulin and PKCdelta in the regulation of the morphology of and trafficking from the early endocytic compartment... - Calmodulin regulates intracellular trafficking of epidermal growth factor receptor and the MAPK signaling pathwayFrancesc Tebar
Departament de Biologia Cel lular, Facultat de Medicina, Institut d Investigacions August Pi i Sunyer IDIBAPS, Universitat de Barcelona, Barcelona, Spain 08036
Mol Biol Cell 13:2057-68. 2002..These data are consistent with the regulation of EGFR by calmodulin at several steps of the receptor signaling and trafficking pathways... - Signaling on the endocytic pathwayMark von Zastrow
Departments of Psychiatry and Cellular and Molecular Pharmacology, University of California at San Francisco, N212E Genentech Hall, Box 2140, UCSF Mission Bay Campus, 600 16th Street, San Francisco, CA 94158, USA
Curr Opin Cell Biol 19:436-45. 2007..General principles of endosome-based signaling are beginning to emerge but, in many cases, the physiological significance of signaling on the endocytic pathway remains poorly understood...