MassIVEapplication/xmlftp://massive.ucsd.edu/v02/MSV000083167/primaryOK2000000ProteomicsJohn D. ScottOrbitrap FusionLTQ Orbitrap EliteHomo Sapiens (ncbitaxon:9606)Mus Musculus (ncbitaxon:10090)https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=15f916a5755e4195add06241191f5d49scottjdw@uw.eduUniversity of Washington, Department of PharmacologyMassIVE2,837UNIMOD:21 - "Phosphorylation."LIP6, ATHSP70, DmErk, extracellular signal-regulated kinase activity, pp44mapk, DSORT, l(2)tumorous imaginal discs, primary tumour of the liver, Tyro5, l(3)L3929, Hsc-4, scd, MEK1/2, raf, adult hepatoma, hepatocellular carcinoma plus intrahepatic cholangiocarcinoma, malignant tumour of liver, p38a, LeMPK3, DmelCG12298, PROTO-LB, p44mpk, Line, Dp38, eosinophilic hepatocellular carcinoma with lamellar fibrosis, SCRAMBLED, Protein Kinases, Kinase, SAPK2, SEM, Sem, FLC, Cyclic AMP Dependent Protein Kinases, Protein Kinase A, irp94, p38A, DmelCG6489, FLF, MAP-k, DmelCG18743, C, hsp70 Ba, cAMP Dependent Protein Kinase, Draf-1, pp42, cell process disease, tumor disease, EK5, HSPH2, adult primary hepatocellular carcinoma, liver and intrahepatic biliary tract cancer, HS24/P52, Dsor2, hepatic cancer, DSor1, DSOR1, sem, D-raf1, cAMP-Dependent, Hsp70Bc, Hsp70Bb, cDNA 10D, hsp70 Aa, Cyclic AMP Dependent Protein Kinase, Hsp70Bd, hld4, 5730551F12Rik, medicine, MSJ-1, dj3, DJ3, Human thyroid-anchoring protein 31, DJ4, hepatocellular fibrolamellar carcinoma, fused to, Homo sapiens disease, cAMP-Dependent Protein Kinases, polygonal cell hepatocellular carcinoma with fibrous stroma, ATP Phosphotransferases, hsc70, HA-3, DmMPK2, single organism signaling, 1500017M13Rik, ERK-A, fibrolamellar, Hsp70b, FHCC, Hsp70a, l(2)tud, dpERK, dpErk, l(1)phl, tid, Non-oncogenic Rho GTPase-specific GTP exchange factor, ERK-1, STRUBBELIG, ERK-2, liver Cancers, DmMAPK, PMK-2, dp-ERK, PMK-1, pka-C1, HS24|P52, not genetically inherited, AKAP-Lbc, HSP70Bbb, PMK-3, liver/hepatobiliary cancer, Hsp70B, hepatocellular adenocarcinoma, Hsp70A, Ht31, primary carcinoma of the liver cells, Dm-hsp70, pMAPK, pMapK, carcinoma of liver and IBT, fibrolamellar variant of hepatocellular carcinoma, DMEK-1, D-MPK2, l(2)td, MADS BOX PROTEIN FLOWERING LOCUS F, ARABIDOPSIS HEAT SHOCK PROTEIN 70, pka-c1, activation, AKAP-13, EK1-1, DmelCG4264, DmelCG5475, DmERKA, liver and intrahepatic bile duct carcinoma, l(1)pole hole, rl/MAPK, c-lbc, Adenosine Cyclic Monophosphate-Dependent Protein Kinases, INSDC_feature:gene, l(2)41Ac, cAMP Dependent Protein Kinases, l(1)polehole, D-raf, Mtap2k, C78273, neoplasm of liver, hsp-70, CT34260, DmelCG4379, dpERk, cancer of liver and intrahepatic biliary tract, PkaC1, Hsp70A7d, PKAcA, dhsp70, Cells, SAPK, Cancer of liver, mDj3, HSC70-4, Mouse, Afr-1, EG:BACH48C10.3, fused, CG31449, other neoplasm, cancer, PKAC1, CG5834, 9030612K14Rik, l(3)j7A4, p44erk1, D-p38 MAPK, Cyclic AMP-Dependent Protein Kinase, resectable malignant neoplasm of the liver, 12559, DRaf, hs70, LBC oncogene, PKA-C1, hepatoblastoma caused by somatic mutation, AFR1, T31P16_130, Afr1, draf, hepatocellular carcinoma, bs17d06.y1, PRO3015, EK2-1, 87A, AA407128, dMPK2, hsp70RY, DMHSP7A2, l(2)cos[[1]], fibrolamellar carcinoma, disease or disorder, Prkm1, Prkm3, neoplasm, hsp70Bb-prime, D-RAF, D-Raf, ERK, Erk, PRKM1, PRKM3, PRKM2, Pka-C, mKIAA0854, p38Ka, primary malignant neoplasm of Liver, DMHSP7D1, nucleoplasmin ATPase activity, ligand, BAP74, mei-1794, Hsp 70, PCBC, Phl, fibrolamellar oncocytic hepatoma, malignant neoplasm of liver, MEK 7, Breast cancer nuclear receptor-binding auxiliary protein, CG31359, cAMP Protein Kinase, Hsc70, CG5504, CG31354, erk, Adenosine Cyclic Monophosphate Dependent Protein Kinases, drugs, Resectable malignant neoplasm of Liver, Cos, Lymphoid blast crisis oncogene, dnajb6, CdkA, hepatocellular carcinoma (fibrolamellar variant), groel, HSC70, liver cell carcinoma, Hsp-70Aa, Hepatic, Draf, rll, carcinoma, STK26, SOR, Sor, Hsc4p, p38-2, myelin basic protein kinase activity, CG31366, Cancer, signalling., oncocytic hepatocellular tumor, PKA Cl, inhibitors, Dp38a, DRT, Esrk1, Hepatic Cancers, LBC, raf-1, disorders, stress-activated kinase activity, MAP-2 kinase activity, eosinophilic glassy cell hepatoma, sor, function, Hsp70ab, Cell, MK, hsp70A, E(csp)1545, hsp70B, neoplastic growth, pkA, PKA, Pka, hsc70-4, stress-activated protein kinase activity, mapk2, mapk1, hepatocellular carcinoma with increased stromal fibrosis, Neoplasm, condition, Mek, MEK, Protein kinase A-anchoring protein 13, AGAMOUS-like 25, cpn60, hsp70a, hsp70b, dhsp70Aa, l(3)03550, pka, pka C1, pKA, CG12559, hirip4, primary carcinoma of liver cells, P42MAPK, i190, Dub, dpERK1, mek, HIRIP4, chaperonin, Cancers, malignant tumor of liver, disease of cellular proliferation, signalling, primary malignant liver neoplasm, l(1)polehole/draf, PKA CI, DmHSP70AA, AU018647, signalling process, Ca liver - primary, dpMAPK, DmelCG5504, l(2)01272, LIVER NEOPL, DmelCG31449, cAMP-Dependent Protein Kinase, Hsp70Bbc, ph, liver cancer, p44mapk, HSP70Bc, SAP kinase activity, Hsp70aB, 6353, dsor1, BRX, FLOWERING LOCUS C, FLOWERING LOCUS F, neoplasia, Mpk2, Hsp70, DnaJ, DNAJ, D-MEK/Dsor, Hepatocyte, p42mapk, heat shock protein 70, D-p38, hepatic, PRKMK7, AGL25, dnaj, p38 alpha, primary liver cancer, SR2-1, SUB, HSP70, APG-2, P44ERK1, diseases, Hepatic Cell, Hsp110, Su(Raf)34B, diseases and disorders, mitogen-activated protein kinase activity, mpk2, mpk1, KIF20A, 2010206B19Rik, not specified as primary or secondary, human disease, Hepatic Cancer, Erk/Map kinase, RY, DmelCG5834, cAMP, liver and intrahepatic bile duct cancer, hsc4, neoplasm (disease), CG4379, DERK-A, xhsp70, DmelCG31359, E(sina)7, Rl, fibrolamellar carcinoma of the liver cells, PROTO-LBC, cancer of liver, MP kinase activity, DERK, GRP78, Dmp38a, signaling process, hepatoblastoma, MBP kinase II activity, ATP - protein phosphotransferase (MAPKK-activated) activity, DmelCG31366, dERK, CG4264, tumor, house mouse, dSor1, CG5475, hepatic neoplasm, ATP, liver Cancer, MNK1, Mnk1, cancer of the liver, MAP kinase 2 activity, SAPKK4, sor/MEK1, dHsp70, D-sor-1, Mapk, rdj2, mouse, primary cancer of liver, DSor, Erk1, ERK1, ERK2, mapk1a, Erk2, FL-HCC, neoplastic disease, HSJ-2, somatic, DRODSOR1, D-P38a, Hepatic Cells, D-p38a, primary liver carcinoma, p41mapk, liver and intrahepatic biliary tract carcinoma, batch, HCC, MapK, mapk1b, MAPK, Cos-1, Diseases, P38, fibrolamellar hepatocellular carcinoma, carcinoma of the liver cells, DRaf1, fibrolamellar carcinoma of liver cells, erk2, dSor, mapk, HSC4, Hsc4, Lines, l(1)G0475, ERKa, Transphosphorylases, BcDNA:RE08694, l(2R)EMS45-39, non-resectable primary hepatic malignant neoplasm, Hsp70-Ab, Hsp70-BC, mice, Draf1, raf1, CAPB, Guanine nucleotide exchange factor Lbc, DmelCG12559, p38, dja2, merged with, DpErk, DpERK, dMEK, ErkA, disease, ERKA, HUMKER1A, dPKA, p41, p40, P44MAPK, p44, Dsor, p47, C110, CG6489, Dcpk, Protein Kinase, RDJ2, pERK, cpr3, rafl, AT1G11140, Resectable malignant neoplasm of liver, other disease, HDJ3, MAPKK7, biological signaling, hepatoma, NEOPL LIVER, GroupII, T31P16.130, l(2)701, DNJ3, hsp70(87A), hsp70Ab, HEL-S-5a, hsp70Aa, ATP phosphohydrolase (polypeptide-unfolding), D-mek, CG12298, Hsp70-1, dp38a, liver, Hek5, HS44KDAP, chaperonin ATPase activity, Dmek, non-chaperonin molecular chaperone ATPase activity, liver cell cancer (hepatocellular carcinoma), hsp70Ba, hsp70Bc, p42-MAPK, DJA2, BG02142, hsp70Bb, JNKK2, Phosphotransferase, dnj3, Hsp-c4, CG15793, Raf1, dhsc70, primary, liver cell fibrolamellar carcinoma, MRJ, DmelCG2845, MKK7, xp42, peroxisome-assembly ATPase activity, Cancer of the liver, CPR3, HSJ2, inhibiteur, Hepatic Neoplasms, PKAc, Transphosphorylase, D-sor, p42 mitogen-activated protein kinase activity, hsp70 87A, CG18732, hsp70 87C, ATP:protein phosphotransferase (MAPKK-activated) activity, non-neoplastic, hsj2, polygonal cell type hepatocellular carcinoma with fibrous Stroma, Erk-1, malignant hepato-biliary neoplasm, fibrolamellar cancer, inhibidor, primary malignant neoplasm of liver, l(1)raf, hepatocellular, Dc0, anon-WO0118547.237, disorder, HHDJ1, DmERK-A, SRF9, fibrolamellar hepatocarcinoma, DRIP78, D-Mek, D-MEK, ert1, Cos1, l(2)s4402, DMPK2, primary tumor of the liver, malignant, drug, DC0, TID56, prkm2, Cell Lines, CT39192, prkm1, carcinoma of liver cells, inhibitor, l(1)2Fe, malignant liver neoplasm, medical condition, Phosphotransferases, STRUBBELIG-RECEPTOR FAMILY 9, MEK/Dsor1, ARHGEF13, p38delta, HSC-70, cos1, Raf/phl, hsp68, Mus, hsp65, group 2, MBP kinase I activity, Dnaj3, dcO, DCO, Dco, hsp70, rare (European definition), LGMD1D, Hsp70(87C), LGMD1E, hepatocellular cancer, CG18743, D-SOR, D-Sor, Xp42, Hsp70.1, DmelCG15793, l(2)tumorous disc, ca liver - primary, spg13, MAPKK, childhood type, mitogen activated kinase activity, Kinases, E(nd)195, Su(Raf)2B, hsp60, PRKA13, dco, SAPKK-4, EY2-2, MAPK2, l(1)ph, MAPK1, 11-29, dp38, cancer of the liver and intrahepatic biliary tract, D-ERK, oncocytic hepatocellular tumour, Ert2, ERT1, hsp 70, ERT2, joined with, EPHT3, p44-MAPK, carcinoma of liver, p44-ERK1, liver carcinoma, RAF, Raf, T19D16.8, coalesced, SCM, MAP kinase 1 activity, CG2845cpr3, LIP6, 6353, HDJ3, l(2)tumorous imaginal discs, DnaJ, l(2)701, DNAJ, DNJ3, PKA-C1, dnaj, hepatocellular carcinoma, PRO3015, l(2)cos[[1]], fibrolamellar carcinoma, eosinophilic hepatocellular carcinoma with lamellar fibrosis, DJA2, BG02142, dnj3, 2010206B19Rik, liver cell fibrolamellar carcinoma, C, MRJ, Pka-C, CG4379, CPR3, HSJ2, fibrolamellar oncocytic hepatoma, PKAc, fibrolamellar carcinoma of the liver cells, CG5504, cDNA 10D, hsj2, polygonal cell type hepatocellular carcinoma with fibrous Stroma, Cos, dnajb6, 5730551F12Rik, fibrolamellar cancer, CdkA, hepatocellular carcinoma (fibrolamellar variant), MSJ-1, dj3, DJ3, DJ4, Dc0, hepatocellular fibrolamellar carcinoma, HHDJ1, polygonal cell hepatocellular carcinoma with fibrous stroma, fibrolamellar hepatocarcinoma, DRIP78, 1500017M13Rik, PKA Cl, oncocytic hepatocellular tumor, fibrolamellar, FHCC, l(2)tud, Cos1, l(2)s4402, tid, rdj2, DC0, TID56, FL-HCC, function, eosinophilic glassy cell hepatoma, HSJ-2, pka-C1, not genetically inherited, cos1, pkA, PKA, Pka, Cos-1, hepatocellular carcinoma with increased stromal fibrosis, Dnaj3, dcO, DCO, Dco, FLC., fibrolamellar variant of hepatocellular carcinoma, l(2)td, fibrolamellar hepatocellular carcinoma, LGMD1D, LGMD1E, pka-c1, fibrolamellar carcinoma of liver cells, l(2)tumorous disc, pka, pka C1, pKA, hirip4, dco, HIRIP4, dja2, PKA CI, DmelCG4379, oncocytic hepatocellular tumour, DmelCG5504, dPKA, PkaC1, l(2)01272, PKAcA, mDj3, Dcpk, RDJ2, PKAC10trueAn acquired scaffolding function of the DNAJ-PKAc fusion enhances oncogenesis in Fibrolamellar carcinomaFibrolamellar carcinoma (FLC) is a rare liver cancer. FLC tumors exclusively produce DNAJ-PKAc, a de novo chimeric enzyme consisting of a chaperonin-binding domain fused to the C subunit of protein kinase A. Biochemical analyses of clinical samples reveal that a unique property of DNAJ-PKAc is the ability to recruit heat shock protein 70 (Hsp70). This cellular chaperonin is frequently up-regulated in cancers. Gene-editing of mouse hepatocytes generated disease-relevant AML12DNAJ-PKAc cell lines. Drug-screening discovered Hsp70 and MEK inhibitor combinations that selectively block proliferation of AML12DNAJ-PKAc cells. Further analyses indicate that the proto-oncogene AKAP-Lbc is upregulated in FLC and functions to cluster DNAJ-PKAc/Hsp70 sub-complexes with a RAF-MEK-ERK kinase module. Phosphoproteomic profiling infers that DNAJ-PKAc biases the signaling landscape toward ERK activation and mobilizes other downstream kinase cascades. We propose that the oncogenic nature of DNAJ-PKAc proceeds through an acquired scaffolding function that permits recruitment of Hsp70 and stabilizes ERK signaling.Tue Nov 27 11:15:00 GMT 2018MSV000083167