![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
GP Briley, MA Hissong, ML Chiu and DC Lee
University of North Carolina, Lineberger Comprehensive Cancer Center 27599-7295, USA.
Soluble forms of transforming growth factor-alpha (TGF alpha) are derived by proteolytic processing of an integral membrane glycoprotein precursor (pro TGF alpha). Previous studies indicated that phorbol ester-induced cleavage of pro TGF alpha in CHO cells is dependent on the presence of a valine residue located at the carboxyl terminus of the precursor's cytoplasmic domain. We reassessed this requirement with epitope-tagged constructs introduced into transformed rat liver epithelial cells that normally express and process TGF alpha. We found that pro TGF alpha mutants lacking the terminal valine residues showed greatly reduced maturation to the fully glycosylated form. Additionally, they were present at substantially reduced levels on the cell surface and, instead, accumulated in the endoplasmic reticulum. Consistent with these results, enzyme-linked immunosorbent assay (ELISA) and Western blot analyses revealed little or no soluble TGF alpha in medium conditioned by cells expressing the mutant constructs. Finally, a truncated pro TGF alpha mutant lacking most of the cytoplasmic domain but retaining a carboxyl-terminal valine was processed and cleaved in a near-normal manner. These results, some of which were reproduced in CHO cells, indicate that the predominant effect of the carboxyl-terminal valines is to ensure normal maturation and routing of the precursor.
This article has been cited by other articles:
|
|
 |
|
  C. Li, M. Hao, Z. Cao, W. Ding, R. Graves-Deal, J. Hu, D. W. Piston, and R. J. Coffey Naked2 Acts as a Cargo Recognition and Targeting Protein to Ensure Proper Delivery and Fusion of TGF-{alpha} containing Exocytic Vesicles at the Lower Lateral Membrane of Polarized MDCK Cells Mol. Biol. Cell, August 1, 2007; 18(8): 3081 - 3093. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Montero, R. Rodriguez-Barrueco, L. Yuste, P. P. Juanes, J. Borges, A. Esparis-Ogando, and A. Pandiella The Extracellular Linker of pro-Neuregulin-{alpha}2c Is Required for Efficient Sorting and Juxtacrine Function Mol. Biol. Cell, February 1, 2007; 18(2): 380 - 393. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Horiuchi, S. Le Gall, M. Schulte, T. Yamaguchi, K. Reiss, G. Murphy, Y. Toyama, D. Hartmann, P. Saftig, and C. P. Blobel Substrate Selectivity of Epidermal Growth Factor-Receptor Ligand Sheddases and their Regulation by Phorbol Esters and Calcium Influx Mol. Biol. Cell, January 1, 2007; 18(1): 176 - 188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Theos, J. F. Berson, S. C. Theos, K. E. Herman, D. C. Harper, D. Tenza, E. V. Sviderskaya, M. L. Lamoreux, D. C. Bennett, G. Raposo, et al. Dual Loss of ER Export and Endocytic Signals with Altered Melanosome Morphology in the silver Mutation of Pmel17 Mol. Biol. Cell, August 1, 2006; 17(8): 3598 - 3612. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. H. Boyle, A. K. Gillingham, S. Munro, and J. Trowsdale Selective Export of HLA-F by Its Cytoplasmic Tail. J. Immunol., June 1, 2006; 176(11): 6464 - 6472. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Martinez-Arca, J. J. Bech-Serra, M. Hurtado-Kuttner, A. Borroto, and J. Arribas Recycling of Cell Surface Pro-transforming Growth Factor-{alpha} Regulates Epidermal Growth Factor Receptor Activation J. Biol. Chem., November 4, 2005; 280(44): 36970 - 36977. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Dong, L. K. Opresko, W. Chrisler, G. Orr, R. D. Quesenberry, D. A. Lauffenburger, and H. S. Wiley The Membrane-anchoring Domain of Epidermal Growth Factor Receptor Ligands Dictates Their Ability to Operate in Juxtacrine Mode Mol. Biol. Cell, June 1, 2005; 16(6): 2984 - 2998. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Paulhe, B. A. Imhof, and B. Wehrle-Haller A Specific Endoplasmic Reticulum Export Signal Drives Transport of Stem Cell Factor (Kitl) to the Cell Surface J. Biol. Chem., December 31, 2004; 279(53): 55545 - 55555. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. M. Myhre, M. Toruner, S. Abraham, and L. J. Egan Metalloprotease disintegrin-mediated ectodomain shedding of EGFR ligands promotes intestinal epithelial restitution Am J Physiol Gastrointest Liver Physiol, December 1, 2004; 287(6): G1213 - G1219. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. L. Tsakadze, U. Sen, Z. Zhao, S. D. Sithu, W. R. English, and S. E. D'Souza Signals mediating cleavage of intercellular adhesion molecule-1 Am J Physiol Cell Physiol, July 1, 2004; 287(1): C55 - C63. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Hinkle, S. W. Sunnarborg, D. Loiselle, C. E. Parker, M. Stevenson, W. E. Russell, and D. C. Lee Selective Roles for Tumor Necrosis Factor {alpha}-converting Enzyme/ADAM17 in the Shedding of the Epidermal Growth Factor Receptor Ligand Family: THE JUXTAMEMBRANE STALK DETERMINES CLEAVAGE EFFICIENCY J. Biol. Chem., June 4, 2004; 279(23): 24179 - 24188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Li, J. L. Franklin, R. Graves-Deal, W. G. Jerome, Z. Cao, and R. J. Coffey Myristoylated Naked2 escorts transforming growth factor {alpha} to the basolateral plasma membrane of polarized epithelial cells PNAS, April 13, 2004; 101(15): 5571 - 5576. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. LEE, S. W. SUNNARBORG, C. L. HINKLE, T. J. MYERS, M. STEVENSON, W. E. RUSSELL, B. J. CASTNER, M. J. GERHART, R. J. PAXTON, R. A. BLACK, et al. TACE/ADAM17 Processing of EGFR Ligands Indicates a Role as a Physiological Convertase Ann. N.Y. Acad. Sci., May 1, 2003; 995(1): 22 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. W. Sunnarborg, C. L. Hinkle, M. Stevenson, W. E. Russell, C. S. Raska, J. J. Peschon, B. J. Castner, M. J. Gerhart, R. J. Paxton, R. A. Black, et al. Tumor Necrosis Factor-alpha Converting Enzyme (TACE) Regulates Epidermal Growth Factor Receptor Ligand Availability J. Biol. Chem., April 5, 2002; 277(15): 12838 - 12845. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Nufer, S. Guldbrandsen, M. Degen, F. Kappeler, J.-P. Paccaud, K. Tani, and H.-P. Hauri Role of cytoplasmic C-terminal amino acids of membrane proteins in ER export J. Cell Sci., January 2, 2002; 115(3): 619 - 628. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Merlos-Suarez, S. Ruiz-Paz, J. Baselga, and J. Arribas Metalloprotease-dependent Protransforming Growth Factor-alpha Ectodomain Shedding in the Absence of Tumor Necrosis Factor-alpha -converting Enzyme J. Biol. Chem., December 14, 2001; 276(51): 48510 - 48517. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kabore, W. Wang, S. Russo, and M. Beers Biosynthesis of surfactant protein C: characterization of aggresome formation by EGFP chimeras containing propeptide mutants lacking conserved cysteine residues J. Cell Sci., January 1, 2001; 114(2): 293 - 302. [Abstract] [PDF]
|
|
|
|
|
|
J. R. Doedens and R. A. Black Stimulation-induced Down-regulation of Tumor Necrosis Factor-alpha Converting Enzyme J. Biol. Chem., May 5, 2000; 275(19): 14598 - 14607. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Reddy, J. L. Slack, R. Davis, D. P. Cerretti, C. J. Kozlosky, R. A. Blanton, D. Shows, J. J. Peschon, and R. A. Black Functional Analysis of the Domain Structure of Tumor Necrosis Factor-alpha Converting Enzyme J. Biol. Chem., May 5, 2000; 275(19): 14608 - 14614. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Bang and C. Kintner Rhomboid and Star facilitate presentation and processing of the Drosophila TGF-alpha homolog Spitz Genes & Dev., January 15, 2000; 14(2): 177 - 186. [Abstract] [Full Text]
|
|
|
|
|
|
J. Dong and H. S. Wiley Trafficking and Proteolytic Release of Epidermal Growth Factor Receptor Ligands Are Modulated by Their Membrane-anchoring Domains J. Biol. Chem., January 7, 2000; 275(1): 557 - 564. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Liu, P. Tzou, R. J. Hill, and P. W. Sternberg Structural Requirements for the Tissue-Specific and Tissue-General Functions of the Caenorhabditis elegans Epidermal Growth Factor LIN-3 Genetics, November 1, 1999; 153(3): 1257 - 1269. [Abstract] [Full Text]
|
|
|
|
|
|
M. L. Saxon and D. C. Lee Mutagenesis Reveals a Role for Epidermal Growth Factor Receptor Extracellular Subdomain IV in Ligand Binding J. Biol. Chem., October 1, 1999; 274(40): 28356 - 28362. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Kapur, R. Cooper, X. Xiao, M. J. Weiss, P. Donovan, and D. A. Williams The Presence of Novel Amino Acids in the Cytoplasmic Domain of Stem Cell Factor Results in Hematopoietic Defects in Steel17H Mice Blood, September 15, 1999; 94(6): 1915 - 1925. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Urena, A Merlos-Suarez, J Baselga, and J Arribas The cytoplasmic carboxy-terminal amino acid determines the subcellular localization of proTGF-(alpha) and membrane type matrix metalloprotease (MT1-MMP) J. Cell Sci., March 15, 1999; 112(6): 773 - 784. [Abstract] [PDF]
|
|
|
|
 |
|
 Y.-T. Chen, D. B. Stewart, and W. J. Nelson Coupling Assembly of the E-Cadherin/beta -Catenin Complex to Efficient Endoplasmic Reticulum Exit and Basal-lateral Membrane Targeting of E-Cadherin in Polarized MDCK Cells J. Cell Biol., February 22, 1999; 144(4): 687 - 699. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Y. Wang, K. E. Frenzel, D. Wen, and D. L. Falls Transmembrane Neuregulins Interact with LIM Kinase 1, a Cytoplasmic Protein Kinase Implicated in Development of Visuospatial Cognition J. Biol. Chem., August 7, 1998; 273(32): 20525 - 20534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Y. Wang, S. J. Miller, and D. L. Falls The N-terminal Region of Neuregulin Isoforms Determines the Accumulation of Cell Surface and Released Neuregulin Ectodomain J. Biol. Chem., January 19, 2001; 276(4): 2841 - 2851. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Wehrle-Haller and B. A. Imhof Stem Cell Factor Presentation to c-Kit. IDENTIFICATION OF A BASOLATERAL TARGETING DOMAIN J. Biol. Chem., April 13, 2001; 276(16): 12667 - 12674. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Brown, R. J. Coffey, and P. J. Dempsey The Proamphiregulin Cytoplasmic Domain Is Required for Basolateral Sorting, but Is Not Essential for Constitutive or Stimulus-induced Processing in Polarized Madin-Darby Canine Kidney Cells J. Biol. Chem., July 27, 2001; 276(31): 29538 - 29549. [Abstract] [Full Text] [PDF]
|
|
