Alexander Sorkin

Summary

Affiliation: University of Colorado Health Sciences Center
Country: USA

Publications

  1. ncbi Lysosomal targeting of epidermal growth factor receptors via a kinase-dependent pathway is mediated by the receptor carboxyl-terminal residues 1022-1123
    E Kornilova
    Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
    J Biol Chem 271:30340-6. 1996
  2. pmc Coordinated traffic of Grb2 and Ras during epidermal growth factor receptor endocytosis visualized in living cells
    Xuejun Jiang
    Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80111, USA
    Mol Biol Cell 13:1522-35. 2002
  3. pmc 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 endocytosis
    Fangtian Huang
    Department of Pharmacology, University of Colorado Health Sciences Center, Aurora, CO 80045, USA
    Mol Biol Cell 16:1268-81. 2005
  4. ncbi TRKing signals through the Golgi
    Alexander Sorkin
    Department of Pharmacology, University of Colorado Health Sciences Center, Aurora, Colorado 80045 3649, USA
    Sci STKE 2005:pe1. 2005
  5. ncbi Signal transduction and endocytosis: close encounters of many kinds
    Alexander Sorkin
    Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80111, USA
    Nat Rev Mol Cell Biol 3:600-14. 2002
  6. ncbi Ubiquitination without E3
    Alexander Sorkin
    Department of Pharmacology, University of Colorado Health Sciences Center, Aurora, CO 80045, USA
    Mol Cell 26:771-3. 2007
  7. ncbi Endocytosis and intracellular trafficking of ErbBs
    Alexander Sorkin
    Department of Pharmacology, University of Colorado Denver Anschutz Medical Center, Aurora, Colorado 80045 0508, USA
    Exp Cell Res 315:683-96. 2009
  8. pmc Endocytosis and intracellular trafficking of ErbBs
    Alexander Sorkin
    Department of Pharmacology, University of Colorado Denver Anschutz Medical Center, Aurora, Colorado 80045 0508, USA
    Exp Cell Res 314:3093-106. 2008
  9. ncbi Internalization of the epidermal growth factor receptor: role in signalling
    A 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
  10. ncbi Interaction of EGF receptor and grb2 in living cells visualized by fluorescence resonance energy transfer (FRET) microscopy
    A Sorkin
    Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80111, USA
    Curr Biol 10:1395-8. 2000

Collaborators

Detail Information

Publications48

  1. ncbi Lysosomal targeting of epidermal growth factor receptors via a kinase-dependent pathway is mediated by the receptor carboxyl-terminal residues 1022-1123
    E 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...
  2. pmc Coordinated traffic of Grb2 and Ras during epidermal growth factor receptor endocytosis visualized in living cells
    Xuejun 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...
  3. pmc 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 endocytosis
    Fangtian 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...
  4. ncbi TRKing signals through the Golgi
    Alexander Sorkin
    Department of Pharmacology, University of Colorado Health Sciences Center, Aurora, Colorado 80045 3649, USA
    Sci STKE 2005:pe1. 2005
    ....
  5. ncbi Signal transduction and endocytosis: close encounters of many kinds
    Alexander 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...
  6. ncbi Ubiquitination without E3
    Alexander 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...
  7. ncbi Endocytosis and intracellular trafficking of ErbBs
    Alexander 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...
  8. pmc Endocytosis and intracellular trafficking of ErbBs
    Alexander 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...
  9. ncbi Internalization of the epidermal growth factor receptor: role in signalling
    A 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...
  10. ncbi Interaction of EGF receptor and grb2 in living cells visualized by fluorescence resonance energy transfer (FRET) microscopy
    A 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...
  11. ncbi Endocytosis and intracellular sorting of receptor tyrosine kinases
    A Alexander
    Department of Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    Front Biosci 3:d729-38. 1998
    ....
  12. ncbi Cargo recognition during clathrin-mediated endocytosis: a team effort
    Alexander 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...
  13. ncbi Enhanced ubiquitylation and accelerated degradation of the dopamine transporter mediated by protein kinase C
    Manuel 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...
  14. ncbi Multiple molecular determinants in the carboxyl terminus regulate dopamine transporter export from endoplasmic reticulum
    Manuel Miranda
    Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
    J Biol Chem 279:30760-70. 2004
    ....
  15. ncbi 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 trafficking
    Fangtian 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...
  16. pmc Multiple mechanisms collectively regulate clathrin-mediated endocytosis of the epidermal growth factor receptor
    Lai 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...
  17. pmc Recruitment of Uev1B to Hrs-containing endosomes and its effect on endosomal trafficking
    Jason 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...
  18. ncbi Constitutive and protein kinase C-induced internalization of the dopamine transporter is mediated by a clathrin-dependent mechanism
    Tatiana 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...
  19. pmc Endosomal targeting of MEK2 requires RAF, MEK kinase activity and clathrin-dependent endocytosis
    Emilia 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...
  20. pmc Three ubiquitin conjugation sites in the amino terminus of the dopamine transporter mediate protein kinase C-dependent endocytosis of the transporter
    Manuel 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...
  21. ncbi Visualization of Rab5 activity in living cells by FRET microscopy and influence of plasma-membrane-targeted Rab5 on clathrin-dependent endocytosis
    Emilia Galperin
    Department of Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    J Cell Sci 116:4799-810. 2003
    ....
  22. pmc EGF receptor ubiquitination is not necessary for its internalization
    Fangtian 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...
  23. ncbi Oligomerization of dopamine transporters visualized in living cells by fluorescence resonance energy transfer microscopy
    Tatiana 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...
  24. ncbi Differential regulation of EGF receptor internalization and degradation by multiubiquitination within the kinase domain
    Fangtian 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...
  25. ncbi RNA interference screen reveals an essential role of Nedd4-2 in dopamine transporter ubiquitination and endocytosis
    Tatiana 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...
  26. pmc Grb2 regulates internalization of EGF receptors through clathrin-coated pits
    Xuejun 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...
  27. pmc Lysine 63-linked polyubiquitination of the dopamine transporter requires WW3 and WW4 domains of Nedd4-2 and UBE2D ubiquitin-conjugating enzymes
    Arnau 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...
  28. ncbi Epidermal growth factor receptor internalization through clathrin-coated pits requires Cbl RING finger and proline-rich domains but not receptor polyubiquitylation
    Xuejun 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...
  29. pmc Differential subcellular distribution of endosomal compartments and the dopamine transporter in dopaminergic neurons
    Anjali 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...
  30. ncbi Analysis of clathrin-mediated endocytosis of epidermal growth factor receptor by RNA interference
    Fangtian 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...
  31. ncbi Effect of tyrosine kinase inhibitors on clathrin-coated pit recruitment and internalization of epidermal growth factor receptor
    Tatiana 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...
  32. pmc Quantitative analysis of endocytosis and turnover of epidermal growth factor (EGF) and EGF receptor
    Alexander Sorkin
    Department of Pharmacology, University of Colorado Denver Medical School, Aurora, Colorado, USA
    Curr Protoc Cell Biol . 2010
    ....
  33. pmc Negative regulation of dopamine transporter endocytosis by membrane-proximal N-terminal residues
    Tatiana 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...
  34. pmc Cyclin-dependent kinase 5 inhibitors: inhibition of dopamine transporter activity
    David 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...
  35. ncbi Conversion of the monomeric red fluorescent protein into a photoactivatable probe
    Vladislav 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...
  36. ncbi Three-chromophore FRET microscopy to analyze multiprotein interactions in living cells
    Emilia 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...
  37. pmc Protein kinase C-dependent ubiquitination and clathrin-mediated endocytosis of the cationic amino acid transporter CAT-1
    Arnau 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...
  38. pmc RNA interference screen identifies Usp18 as a regulator of epidermal growth factor receptor synthesis
    Jason 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...
  39. ncbi 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...
  40. ncbi Regulation of receptors and transporters by ubiquitination: new insights into surprisingly similar mechanisms
    Manuel 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...
  41. pmc Trafficking of dopamine transporters in psychostimulant actions
    Nancy 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...
  42. pmc Endocytosis and signalling: intertwining molecular networks
    Alexander 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...
  43. pmc Mice expressing markedly reduced striatal dopamine transporters exhibit increased locomotor activity, dopamine uptake turnover rate, and cocaine responsiveness
    Anjali Rao
    Department of Pharmacology, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, 80045
    Synapse 67:668-77. 2013
    ..Hence, these mice represent a unique model for studying changes of in vivo DAT function and regulation that result from markedly reduced levels of DAT expression. Synapse 67:668-677, 2013. © 2013 Wiley Periodicals, Inc. ..
  44. pmc Calmodulin regulates intracellular trafficking of epidermal growth factor receptor and the MAPK signaling pathway
    Francesc 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...
  45. pmc Protein kinaseCdelta-calmodulin crosstalk regulates epidermal growth factor receptor exit from early endosomes
    Anna 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...
  46. ncbi Visualization of Rab5 activity in living cells using FRET microscopy
    Emilia 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...
  47. ncbi Direct interaction of Cbl with pTyr 1045 of the EGF receptor (EGFR) is required to sort the EGFR to lysosomes for degradation
    Lene Melsaether Grøvdal
    Institute of Pathology, University of Oslo, Rikshospitalet, N 0027 Oslo, Norway
    Exp Cell Res 300:388-95. 2004
    ....
  48. pmc Signaling on the endocytic pathway
    Mark 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...