![[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}
|
|
|
|
|
||
HJ Cheng and JG Flanagan
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115.
The kit ligand (KL) is one of several growth factors that are active as transmembrane molecules and can also be proteolytically cleaved to yield soluble forms. We have investigated the signals and structural determinants that control the cleavage of KL. Presentation at the membrane appears to be critical, because no cleavage occurs in variants that lack a transmembrane domain. Signals in the cytoplasmic domain do not seem to be required, because cleavage was not blocked by removal of the C-terminal valine residue, deletion of the whole cytoplasmic tail, or the replacement of the cytoplasmic tail that occurs in the Sl17H mutation. KL thus appears to differ from transforming growth factor- alpha, which apparently requires a C-terminal valine as a signal for cleavage. Although proteolysis must be tightly restricted to the correct cell surface proteins and sites within each protein, cleavage of KL does not seem to be determined entirely by a requirement for a specific substrate sequence. However, the effects of deletion or insertion variants of KL suggest that cleavage may be limited to sites within a specific range of distances from the cell membrane.
This article has been cited by other articles:
|
|
 |
|
  N. Kawaguchi, K. Horiuchi, J. D. Becherer, Y. Toyama, P. Besmer, and C. P. Blobel Different ADAMs have distinct influences on Kit ligand processing: phorbol-ester-stimulated ectodomain shedding of Kitl1 by ADAM17 is reduced by ADAM19 J. Cell Sci., March 15, 2007; 120(6): 943 - 952. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. L. Tsakadze, S. D. Sithu, U. Sen, W. R. English, G. Murphy, and S. E. D'Souza Tumor Necrosis Factor-{alpha}-converting Enzyme (TACE/ADAM-17) Mediates the Ectodomain Cleavage of Intercellular Adhesion Molecule-1 (ICAM-1) J. Biol. Chem., February 10, 2006; 281(6): 3157 - 3164. [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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 M. A. Bedell and A. M. Zama Genetic Analysis of Kit Ligand Functions During Mouse Spermatogenesis J Androl, March 1, 2004; 25(2): 188 - 199. [Full Text] [PDF]
|
|
|
|
|
|
Y. Zheng, J. Schlondorff, and C. P. Blobel Evidence for Regulation of the Tumor Necrosis Factor alpha -Convertase (TACE) by Protein-tyrosine Phosphatase PTPH1 J. Biol. Chem., November 1, 2002; 277(45): 42463 - 42470. [Abstract] [Full Text] [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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
S. de Bernard, M. Misrahi, J.-C. Huet, I. Beau, A. Desroches, H. Loosfelt, C. Pichon, J.-C. Pernollet, and E. Milgrom Sequential Cleavage and Excision of a Segment of the Thyrotropin Receptor Ectodomain J. Biol. Chem., January 1, 1999; 274(1): 101 - 107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Povey, N. Weeratunge, C. Marden, A. Sehgal, A. Thrasher, and C. Casimir Enhanced Retroviral Transduction of 5-Fluorouracil-Resistant Human Bone Marrow (Stem) Cells Using a Genetically Modified Packaging Cell Line Blood, December 1, 1998; 92(11): 4080 - 4089. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Peschon, J. L. Slack, P. Reddy, K. L. Stocking, S. W. Sunnarborg, D. C. Lee, W. E. Russell, B. J. Castner, R. S. Johnson, J. N. Fitzner, et al. An Essential Role for Ectodomain Shedding in Mammalian Development Science, November 13, 1998; 282(5392): 1281 - 1284. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. Sadhukhan, G. C. Sen, R. Ramchandran, and I. Sen The distal ectodomain of angiotensin-converting enzyme regulates its cleavage-secretion from the cell surface PNAS, January 6, 1998; 95(1): 138 - 143. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Arribas, F. Lopez-Casillas, and J. Massague Role of the Juxtamembrane Domains of the Transforming Growth Factor-alpha Precursor and the beta -Amyloid Precursor Protein in Regulated Ectodomain Shedding J. Biol. Chem., July 4, 1997; 272(27): 17160 - 17165. [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]
|
|
|
|
|
|
J. Schlondorff, L. Lum, and C. P. Blobel Biochemical and Pharmacological Criteria Define Two Shedding Activities for TRANCE/OPGL That Are Distinct from the Tumor Necrosis Factor alpha Convertase J. Biol. Chem., April 27, 2001; 276(18): 14665 - 14674. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Tzarfaty-Majar, R. Lopez-Alemany, Y. Feinstein, L. Gombau, O. Goldshmidt, E. Soriano, P. Munoz-Canoves, and A. Klar Plasmin-mediated Release of the Guidance Molecule F-spondin from the Extracellular Matrix J. Biol. Chem., July 20, 2001; 276(30): 28233 - 28241. [Abstract] [Full Text] [PDF]
|
|
