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Mass spectrometry-based proteomics revealed Glypican-1 as a novel ADAM17 substrate.
ADAM17 (a disintegrin and metalloproteinase 17) is a plasma membrane metalloprotease involved in proteolytic release of the extracellular domain of many cell surface molecules, a process known as ectodomain shedding. Through this process, ADAM17 is implicated in several aspects of tumor growth and metastasis in a broad range of tumors, including head and neck squamous cell carcinomas (HNSCC). In this study, mass spectrometry-based proteomics approaches revealed glypican-1 (GPC1) as a new substrate for ADAM17, and its shedding was confirmed to be metalloprotease-dependent, induced by a pleiotropic agent (PMA) and physiologic ligand (EGF), and inhibited by marimastat. In addition, immunoblotting analysis of GPC1 in the extracellular media from control and ADAM17shRNA pointed to a direct involvement of ADAM17 in the cleavage of GPC1. Moreover, mass spectrometry-based interactome analysis of GPC1 revealed biological functions and pathways related mainly to cellular movement, adhesion and proliferation, which were events also modulated by up regulation of full length and cleavage GPC1. Altogether, we showed that GPC1 is a novel ADAM17 substrate, thus the function of GPC1 may be modulated by proteolysis signaling.
Authors : Kawahara Rebeca , Granato Daniela Campos , Yokoo Sami , Domingues Romênia Ramos , Trindade Daniel Maragno , Paes Leme Adriana Franco ,
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Pathways :
WP1029: Notch Signaling Pathway
WP1064: Delta-Notch Signaling Pathway
WP1077: cytochrome P450
WP1180: Delta-Notch Signaling Pathway
WP1194: cytochrome P450
WP1219: cytochrome P450
WP1232: Notch Signaling Pathway
WP1274: cytochrome P450
WP1357: Notch Signaling Pathway
WP1382: Delta-Notch Signaling Pathway
WP1390: cytochrome P450
WP199: Delta-Notch Signaling Pathway
WP2059: Alzheimers Disease
WP2075: Alzheimers Disease
WP265: Delta-Notch Signaling Pathway
WP268: Notch Signaling Pathway
WP29: Notch Signaling Pathway
WP517: Notch Signaling Pathway
WP827: Delta-Notch Signaling Pathway
WP912: Notch Signaling Pathway
WP946: Delta-Notch Signaling Pathway
WP958: cytochrome P450
Related Genes :
[FTO KIAA1752] Alpha-ketoglutarate-dependent dioxygenase FTO (EC 1.14.11.-) (Fat mass and obesity-associated protein)
[Fto Kiaa1752] Alpha-ketoglutarate-dependent dioxygenase FTO (EC 1.14.11.-) (Fat mass and obesity-associated protein) (Protein fatso)
[PSMB8 LMP7 PSMB5i RING10 Y2] Proteasome subunit beta type-8 (EC 3.4.25.1) (Low molecular mass protein 7) (Macropain subunit C13) (Multicatalytic endopeptidase complex subunit C13) (Proteasome component C13) (Proteasome subunit beta-5i) (Really interesting new gene 10 protein)
[PSMB10 LMP10 MECL1] Proteasome subunit beta type-10 (EC 3.4.25.1) (Low molecular mass protein 10) (Macropain subunit MECl-1) (Multicatalytic endopeptidase complex subunit MECl-1) (Proteasome MECl-1) (Proteasome subunit beta-2i)
[DUSP23 LDP3 VHZ] Dual specificity protein phosphatase 23 (EC 3.1.3.16) (EC 3.1.3.48) (Low molecular mass dual specificity phosphatase 3) (LDP-3) (VH1-like phosphatase Z)
[Gpr98 Kiaa0686 Mass1 Vlgr1] G-protein coupled receptor 98 (Monogenic audiogenic seizure susceptibility protein 1) (Neurepin) (Very large G-protein coupled receptor 1)
[GPR98 KIAA0686 KIAA1943 MASS1 VLGR1] G-protein coupled receptor 98 (Monogenic audiogenic seizure susceptibility protein 1 homolog) (Usher syndrome type-2C protein) (Very large G-protein coupled receptor 1)
[Psmb4 Lmp3] Proteasome subunit beta type-4 (EC 3.4.25.1) (Low molecular mass protein 3) (Macropain beta chain) (Multicatalytic endopeptidase complex beta chain) (Proteasome beta chain) (Proteasome chain 3)
[poe calo push CG14472] Protein purity of essence (Interaction calmodulin and colossal molecular mass protein) (Protein Calossin) (Protein pushover)
[PSMB9 LMP2 PSMB6i RING12] Proteasome subunit beta type-9 (EC 3.4.25.1) (Low molecular mass protein 2) (Macropain chain 7) (Multicatalytic endopeptidase complex chain 7) (Proteasome chain 7) (Proteasome subunit beta-1i) (Really interesting new gene 12 protein)
[Psmb6 Lmp19] Proteasome subunit beta type-6 (EC 3.4.25.1) (Low molecular mass protein 19) (Macropain delta chain) (Multicatalytic endopeptidase complex delta chain) (Proteasome delta chain) (Proteasome subunit Y)
[DUSP26 DUSP24 LDP4 MKP8 NATA1 SKRP3] Dual specificity protein phosphatase 26 (EC 3.1.3.16) (EC 3.1.3.48) (Dual specificity phosphatase SKRP3) (Low-molecular-mass dual-specificity phosphatase 4) (DSP-4) (LDP-4) (Mitogen-activated protein kinase phosphatase 8) (MAP kinase phosphatase 8) (MKP-8) (Novel amplified gene in thyroid anaplastic cancer)
[Psmb8 Lmp7 Mc13] Proteasome subunit beta type-8 (EC 3.4.25.1) (Low molecular mass protein 7) (Macropain subunit C13) (Multicatalytic endopeptidase complex subunit C13) (Proteasome component C13) (Proteasome subunit beta-5i)
[Psmb9 Lmp2 Ring12] Proteasome subunit beta type-9 (EC 3.4.25.1) (LMP-2d) (Low molecular mass protein 2) (Macropain chain 7) (Multicatalytic endopeptidase complex chain 7) (Proteasome chain 7) (Proteasome subunit beta-1i) (Really interesting new gene 12 protein)
[Psmb10 Lmp10 Mecl1] Proteasome subunit beta type-10 (EC 3.4.25.1) (Low molecular mass protein 10) (Macropain subunit MECl-1) (Multicatalytic endopeptidase complex subunit MECl-1) (Proteasome MECl-1) (Proteasome subunit beta-2i)
[psbA PCL_7801] Photosystem II protein D1 (PSII D1 protein) (EC 1.10.3.9) (Photosystem II Q(B) protein)
[nnrD nnrE MASS_3753] Multifunctional fusion protein [Includes: ADP-dependent (S)-NAD(P)H-hydrate dehydratase (EC 4.2.1.136) (ADP-dependent NAD(P)HX dehydratase); NAD(P)H-hydrate epimerase (EC 5.1.99.6) (NAD(P)HX epimerase)]
[glmU MASS_1145] Bifunctional protein GlmU [Includes: UDP-N-acetylglucosamine pyrophosphorylase (EC 2.7.7.23) (N-acetylglucosamine-1-phosphate uridyltransferase); Glucosamine-1-phosphate N-acetyltransferase (EC 2.3.1.157)]
[Psmb9 Lmp2 Ring12] Proteasome subunit beta type-9 (EC 3.4.25.1) (Low molecular mass protein 2) (Macropain chain 7) (Multicatalytic endopeptidase complex chain 7) (Proteasome chain 7) (Proteasome subunit beta-1i) (Really interesting new gene 12 protein)
[Dusp23 Ldp3] Dual specificity protein phosphatase 23 (EC 3.1.3.16) (EC 3.1.3.48) (Low molecular mass dual specificity phosphatase 3) (LDP-3)
[M] Membrane protein (M protein) (E1 glycoprotein) (Matrix glycoprotein) (Membrane glycoprotein)
[Psmb9 Lmp2 Ring12] Proteasome subunit beta type-9 (EC 3.4.25.1) (Low molecular mass protein 2) (Macropain chain 7) (Multicatalytic endopeptidase complex chain 7) (Proteasome chain 7) (Proteasome subunit beta-1i) (Really interesting new gene 12 protein)
[Psmb9 Lmp2 Ring12] Proteasome subunit beta type-9 (EC 3.4.25.1) (Low molecular mass protein 2) (Macropain chain 7) (Multicatalytic endopeptidase complex chain 7) (Proteasome chain 7) (Proteasome subunit beta-1i) (Really interesting new gene 12 protein)
[Psmb9 Lmp2 Ring12] Proteasome subunit beta type-9 (EC 3.4.25.1) (Low molecular mass protein 2) (Macropain chain 7) (Multicatalytic endopeptidase complex chain 7) (Proteasome chain 7) (Proteasome subunit beta-1i) (Really interesting new gene 12 protein)
[ribBA MASS_2736] Riboflavin biosynthesis protein RibBA [Includes: 3,4-dihydroxy-2-butanone 4-phosphate synthase (DHBP synthase) (EC 4.1.99.12); GTP cyclohydrolase-2 (EC 3.5.4.25) (GTP cyclohydrolase II)]
[murE MASS_1990] UDP-N-acetylmuramoyl-L-alanyl-D-glutamate--2,6-diaminopimelate ligase (EC 6.3.2.13) (Meso-A2pm-adding enzyme) (Meso-diaminopimelate-adding enzyme) (UDP-MurNAc-L-Ala-D-Glu:meso-diaminopimelate ligase) (UDP-MurNAc-tripeptide synthetase) (UDP-N-acetylmuramyl-tripeptide synthetase)
[Fto] Alpha-ketoglutarate-dependent dioxygenase FTO (EC 1.14.11.-) (Fat mass and obesity-associated protein)
[asd MASS_0339] Aspartate-semialdehyde dehydrogenase (ASA dehydrogenase) (ASADH) (EC 1.2.1.11) (Aspartate-beta-semialdehyde dehydrogenase)
[Psmb9 Lmp2 Ring12] Proteasome subunit beta type-9 (EC 3.4.25.1) (Low molecular mass protein 2) (Macropain chain 7) (Multicatalytic endopeptidase complex chain 7) (Proteasome chain 7) (Proteasome subunit beta-1i) (Really interesting new gene 12 protein)
[prs MASS_1144] Ribose-phosphate pyrophosphokinase (RPPK) (EC 2.7.6.1) (5-phospho-D-ribosyl alpha-1-diphosphate) (Phosphoribosyl diphosphate synthase) (Phosphoribosyl pyrophosphate synthase) (P-Rib-PP synthase) (PRPP synthase) (PRPPase)
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