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PMID: 15197174 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Cell-matrix interaction via CD44 is independently regulated by different metalloproteinases activated in response to extracellular Ca(2+) influx and PKC activation.

The Journal of cell biology ·Vol. 165 ·No. 6 ·2004-06-21 ·Pages 893-902

Nagano O, Murakami D, Hartmann D, De Strooper B, Saftig P, Iwatsubo T, Nakajima M, Shinohara M, Saya H

Abstract

CD44 is an adhesion molecule that interacts with hyaluronic acid (HA) and undergoes sequential proteolytic cleavages in its ectodomain and intramembranous domain. The ectodomain cleavage is triggered by extracellular Ca(2+) influx or the activation of protein kinase C. Here we show that CD44-mediated cell-matrix adhesion is terminated by two independent ADAM family metalloproteinases, ADAM10 and ADAM17, differentially regulated in response to those stimuli. Ca(2+) influx activates ADAM10 by regulating the association between calmodulin and ADAM10, leading to CD44 ectodomain cleavage. Depletion of ADAM10 strongly inhibits the Ca(2+) influx-induced cell detachment from matrix. On the other hand, phorbol ester stimulation activates ADAM17 through the activation of PKC and small GTPase Rac, inducing proteolysis of CD44. Furthermore, depletion of ADAM10 or ADAM17 markedly suppressed CD44-dependent cancer cell migration on HA, but not on fibronectin. The spatio-temporal regulation of two independent signaling pathways for CD44 cleavage plays a crucial role in cell-matrix interaction and cell migration.

MeSH Terms
ADAM Proteins ADAM12 Protein Animals Biological Transport Calcium/metabolism Cell Line Cell-Matrix Junctions/physiology Embryo, Mammalian Enzyme Activation Fibroblasts/physiology,ultrastructure Hyaluronan Receptors/physiology Membrane Proteins/deficiency,genetics,physiology Metalloproteases/metabolism Mice Mice, Knockout Muscle Proteins/deficiency,genetics,physiology Protein Kinase C/metabolism
Chemicals
Hyaluronan Receptors Membrane Proteins Muscle Proteins Protein Kinase C Metalloproteases ADAM Proteins ADAM12 Protein Adam12 protein, mouse Calcium
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Nagano Osamu
Dept. of Tumor Genetics and Biology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
Murakami Daizo
Hartmann Dieter
De Strooper Bart
Saftig Paul
Iwatsubo Takeshi
Nakajima Motowo
Shinohara Masanori
Saya Hideyuki
References (44)
44 references, click to expand
  1. Hyaluronan enters keratinocytes by a novel endocytic route for catabolism.
    J Biol Chem. 2001 Sep 14;276(37):35111-22 PMID: 11451952
  2. Transmembrane collagen XVII, an epithelial adhesion protein, is shed from the cell surface by ADAMs.
    EMBO J. 2002 Oct 1;21(19):5026-35 PMID: 12356719
  3. Presenilin-dependent gamma-secretase activity mediates the intramembranous cleavage of CD44.
    Oncogene. 2003 Mar 13;22(10):1511-6 PMID: 12629514
  4. The liberation of CD44.
    J Cell Biol. 2003 Jun 9;161(5):839-43 PMID: 12796473
  5. Intracellular coupling via limiting calmodulin.
    J Biol Chem. 2003 Jul 4;278(27):24247-50 PMID: 12738782
  6. The disintegrin-like metalloproteinase ADAM10 is involved in constitutive cleavage of CX3CL1 (fractalkine) and regulates CX3CL1-mediated cell-cell adhesion.
    Blood. 2003 Aug 15;102(4):1186-95 PMID: 12714508
  7. TACE/ADAM-17 enzymatic activity is increased in response to cellular stimulation.
    Biochem Biophys Res Commun. 2003 Aug 22;308(2):331-8 PMID: 12901873
  8. Rho and Rac take center stage.
    Cell. 2004 Jan 23;116(2):167-79 PMID: 14744429
  9. Distinct roles for ADAM10 and ADAM17 in ectodomain shedding of six EGFR ligands.
    J Cell Biol. 2004 Mar 1;164(5):769-79 PMID: 14993236
  10. CD44 structure and function.
    Front Biosci. 1998 Jul 1;3:d616-30 PMID: 9634544
  11. Control of cell shape and locomotion by external calcium.
    Exp Cell Res. 1984 Oct;154(2):412-20 PMID: 6541148
  12. CD44 is the principal cell surface receptor for hyaluronate.
    Cell. 1990 Jun 29;61(7):1303-13 PMID: 1694723
  13. A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells.
    Cell. 1991 Apr 5;65(1):13-24 PMID: 1707342
  14. Expression of proteoglycans and hyaluronan during wound healing.
    J Histochem Cytochem. 1995 Feb;43(2):125-35 PMID: 7529785
  15. Identification of IQGAP as a putative target for the small GTPases, Cdc42 and Rac1.
    J Biol Chem. 1996 Sep 20;271(38):23363-7 PMID: 8798539
  16. CD44 phosphorylation regulates melanoma cell and fibroblast migration on, but not attachment to, a hyaluronan substratum.
    Curr Biol. 1996 Jul 1;6(7):884-90 PMID: 8805300
  17. Calcium influx inhibits MT1-MMP processing and blocks MMP-2 activation.
    FEBS Lett. 1997 Aug 4;412(3):568-72 PMID: 9276468
  18. Identification and characterization of a pro-tumor necrosis factor-alpha-processing enzyme from the ADAM family of zinc metalloproteases.
    J Biol Chem. 1997 Sep 26;272(39):24588-93 PMID: 9305925
  19. Cytosolic calmodulin is increased in SK-N-SH human neuroblastoma cells due to release of calcium from intracellular stores.
    J Neurochem. 1998 Jan;70(1):139-46 PMID: 9422356
  20. Calmodulin regulates L-selectin adhesion molecule expression and function through a protease-dependent mechanism.
    Cell. 1998 Mar 20;92(6):809-18 PMID: 9529256
  21. Extracellular calcium influx stimulates metalloproteinase cleavage and secretion of heparin-binding EGF-like growth factor independently of protein kinase C.
    J Cell Biochem. 1998 May 1;69(2):143-53 PMID: 9548562
  22. TNF-alpha converting enzyme (TACE) is inhibited by TIMP-3.
    FEBS Lett. 1998 Sep 11;435(1):39-44 PMID: 9755855
  23. Evidence that tumor necrosis factor alpha converting enzyme is involved in regulated alpha-secretase cleavage of the Alzheimer amyloid protein precursor.
    J Biol Chem. 1998 Oct 23;273(43):27765-7 PMID: 9774383
  24. CD44 cleavage induced by a membrane-associated metalloprotease plays a critical role in tumor cell migration.
    Oncogene. 1999 Feb 18;18(7):1435-46 PMID: 10050880
  25. Hormone-induced secretory and nuclear translocation of calmodulin: oscillations of calmodulin concentration with the nucleus as an integrator.
    Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4426-31 PMID: 10200278
  26. Mechanism of Ca2+-dependent nuclear accumulation of calmodulin.
    Proc Natl Acad Sci U S A. 1999 May 25;96(11):6217-22 PMID: 10339568
  27. Regulation of cell movement is mediated by stretch-activated calcium channels.
    Nature. 1999 Jul 22;400(6742):382-6 PMID: 10432119
  28. Regulated CD44 cleavage under the control of protein kinase C, calcium influx, and the Rho family of small G proteins.
    J Biol Chem. 1999 Sep 3;274(36):25525-34 PMID: 10464284
  29. Metalloprotease-disintegrins: modular proteins capable of promoting cell-cell interactions and triggering signals by protein-ectodomain shedding.
    J Cell Sci. 1999 Nov;112 ( Pt 21):3603-17 PMID: 10523497
  30. Ras oncoprotein induces CD44 cleavage through phosphoinositide 3-OH kinase and the rho family of small G proteins.
    J Biol Chem. 2000 Sep 22;275(38):29628-35 PMID: 10896935
  31. Calcium influx triggers the sequential proteolysis of extracellular and cytoplasmic domains of E-cadherin, leading to loss of beta-catenin from cell-cell contacts.
    Oncogene. 1999 Nov 25;18(50):7080-90 PMID: 10597309
  32. CD44 interaction with tiam1 promotes Rac1 signaling and hyaluronic acid-mediated breast tumor cell migration.
    J Biol Chem. 2000 Jan 21;275(3):1829-38 PMID: 10636882
  33. Stimulation of cleavage of membrane proteins by calmodulin inhibitors.
    Biochem J. 2000 Mar 1;346 Pt 2:359-67 PMID: 10677354
  34. The in vitro activity of ADAM-10 is inhibited by TIMP-1 and TIMP-3.
    FEBS Lett. 2000 May 19;473(3):275-9 PMID: 10818225
  35. Shedding of c-Met is regulated by crosstalk between a G-protein coupled receptor and the EGF receptor and is mediated by a TIMP-3 sensitive metalloproteinase.
    J Cell Sci. 2001 Mar;114(Pt 6):1213-20 PMID: 11228164
  36. Membrane-type 1 matrix metalloproteinase cleaves CD44 and promotes cell migration.
    J Cell Biol. 2001 May 28;153(5):893-904 PMID: 11381077
  37. Regulation of the alpha-secretase ADAM10 by its prodomain and proprotein convertases.
    FASEB J. 2001 Aug;15(10):1837-9 PMID: 11481247
  38. Proteolytic release of CD44 intracellular domain and its role in the CD44 signaling pathway.
    J Cell Biol. 2001 Nov 26;155(5):755-62 PMID: 11714729
  39. Proteolytic cleavage of the CD44 adhesion molecule in multiple human tumors.
    Am J Pathol. 2002 Feb;160(2):441-7 PMID: 11839564
  40. Extracellular signal-regulated kinase phosphorylates tumor necrosis factor alpha-converting enzyme at threonine 735: a potential role in regulated shedding.
    Mol Biol Cell. 2002 Jun;13(6):2031-44 PMID: 12058067
  41. Polarized calcium and calmodulin signaling in secretory epithelia.
    Physiol Rev. 2002 Jul;82(3):701-34 PMID: 12087133
  42. The metalloprotease Kuzbanian (ADAM10) mediates the transactivation of EGF receptor by G protein-coupled receptors.
    J Cell Biol. 2002 Jul 22;158(2):221-6 PMID: 12119356
  43. The disintegrin/metalloprotease ADAM 10 is essential for Notch signalling but not for alpha-secretase activity in fibroblasts.
    Hum Mol Genet. 2002 Oct 1;11(21):2615-24 PMID: 12354787
  44. The disintegrins ADAM10 and TACE contribute to the constitutive and phorbol ester-regulated normal cleavage of the cellular prion protein.
    J Biol Chem. 2001 Oct 12;276(41):37743-6 PMID: 11477090
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200310024
Published
2004-06-21
Epub
2004-00-14
Pages
893-902
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2172408
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200310024 PMC Full Text View journal details
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