1. Figure S1 and Table S1 Exposure of human monocytes to oxLDL leads to rapid changes in proteins phosphorylation status Human monocytes treated for 5,15 and 30 min. with oxLDL (25  g/ml), respectively were lysed, enriched for phosphoproteins, labeled with TMT 127 (oxLDL treated samples) and TMT 126 label (control cells), digested into peptides and analyzed as described in “Methods” section using semi-quantitative phosphoprotemics. Table 1 shows a complete list of peptides identified applying selection criteria in detail described in “Methods” section. The amount of identified peptides increased over time and their relative quantity after treatment with oxLDL was calculated based on TMT 127/126 ratio. In red are depicted peptides that have shown increased TMT 127/126 ratio, in green peptides with decreased ratio. Fold change of 1.8 was set up as a cut-off value.

2. oxLDL 5min Number of peptides identified oxLDL 15min Number of peptides identified oxLDL 30min Number of peptides identified Accession number Description127/126 P15531Nucleoside diphosphate kinase A3.8415.119.52 P22392Nucleoside diphosphate kinase B3.856.748.65 P50502Hsc70-interacting protein10.214.916.62 P28676Grancalcin1.331.516.35 Q1344228 kDa heat- and acid-stable phosphoprotein2.313.515.51 P25786Proteasome subunit alpha type-12.81 34.44 P22234Multifunctional protein ADE21.411.324.11 Q01518Adenylyl cyclase-associated protein 11.643.91049 O60610Protein diaphanous homolog 12.121.853.95 Q9BRF8Calcineurin-like phosphoesterase domain- containing protein 1 1.112.213.72 P04114Apolipoprotein B-1006.135.5203.718 P12956X-ray repair cross-complementing protein 61.015.043.611 O60234Glia maturation factor gamma4.413.413.11 P07437Tubulin beta chain1.713.333.12 O14818Proteasome subunit alpha type-72.912.4332 Q9HDC9Adipocyte plasma membrane-associated protein 1.412.8335 P05141ADP/ATP translocase 21.111.822.83 P06454Prothymosin alpha4.953.632.84 P22626Heterogeneous nuclear ribonucleoproteins A2/B1 1.95 122.811 P28066Proteasome subunit alpha type-51.711.412.73 Q14152Eukaryotic translation initiation factor 3 subunit A 1.121.082.67 P14625Endoplasmin1.431.5142.614 P07237Protein disulfide-isomerase2.153.4122.517 P35232Prohibitin1.842.282.46 Q99623Prohibitin-22.223.272.47 O75533Splicing factor 3B subunit 1112.222.42 P12036Neurofilament heavy polypeptide1.421.212.32 P68366Tubulin alpha-4A chain151.412.313 Q14764Major vault protein2.411.752.27 Q6DD88Atlastin-31.612.312.23 P31153S-adenosylmethionine synthase isoform type-2121.822.22 P6198114-3-3 protein gamma1.211.612.12 P05496ATP synthase lipid-binding protein, mitochondrial 1.511.912.11 Q9H3G5Probable serine carboxypeptidase CPVL1.111.2124 P53396ATP-citrate synthase1.121.313214 P13010X-ray repair cross-complementing protein 52.221.3627 P3599826S protease regulatory subunit 72.421.9222 Q13185Chromobox protein homolog 31.812.1322

3. oxLDL 5min Number of peptides identified oxLDL 15min Number of peptides identified oxLDL 30min Number of peptides identified Accession number Description127/126 Q00610Clathrin heavy chain 11.312.515220 P11413Glucose-6-phosphate 1-dehydrogenase122.491.914 Q05655Protein kinase C delta type1.211.351.96 P26641Elongation factor 1-gamma1.361.671.89 O15143Actin-related protein 2/3 complex subunit 1B1.83 5 5 Q96D96Voltage-gated hydrogen channel 12.212.811.72 P31948Stress-induced-phosphoprotein 11.12291.79 P07910Heterogeneous nuclear ribonucleoproteins C1/C2 1.222.341.64 O75351Vacuolar protein sorting-associated protein 4B 1.422.311.61 P6219126S protease regulatory subunit 42.211.221.51 P08107Heat shock 70 kDa protein 1A/1B2.251.371.410 Q92688Acidic leucine-rich nuclear phosphoprotein 32 family member B 2.61221.41 P13796Plastin-22.512.721.41 Q02750Dual specificity mitogen-activated protein kinase kinase 1 1.811.221.45 P60842Eukaryotic initiation factor 4A-I1.212.221.41 P1798026S protease regulatory subunit 6A1.412.521.31 P52565Rho GDP-dissociation inhibitor 12.211.24 2 P60709Actin, cytoplasmic 11.782.421.24 O4324226S proteasome non-ATPase regulatory subunit 3 2.312.421.12 P13667Protein disulfide-isomerase A40.9120.7120.512 P50570Dynamin-20.81 60.55 P54136Arginyl-tRNA synthetase, cytoplasmic0.710.53 5 P31689DnaJ homolog subfamily A member 1110.52 2 P54577Tyrosyl-tRNA synthetase, cytoplasmic0.81 30.51 O75582Ribosomal protein S6 kinase alpha-50.920.610.51 Q8N684Cleavage and polyadenylation specificity factor subunit 7 0.910.51 1 Q8ND76Cyclin-Y110.510.41 P63241Eukaryotic translation initiation factor 5A-10.93 70.46 O14773Tripeptidyl-peptidase 1110.720.42 Q96L92Sorting nexin-270.910.520.43 P32119Peroxiredoxin-2110.910.41 Q07065Cytoskeleton-associated protein 40.9190.5150.413 Q13464Rho-associated protein kinase 10.930.43 1 P62318Small nuclear ribonucleoprotein Sm D30.810.910.42 Q7L591Docking protein 30.910.42 3 O14745Na(+)/H(+) exchange regulatory cofactor NHE-RF1 0.890.5110.49 P04083Annexin A10.8650.6810.478

4. oxLDL 5min Number of peptides identified oxLDL 15min Number of peptides identified oxLDL 30min Number of peptides identified AccessionDescription127/126 Q15233Non-POU domain-containing octamer-binding protein 0.92130.45 Q8NBS9Thioredoxin domain-containing protein 5140.46 8 P37108Signal recognition particle 14 kDa protein0.720.520.41 A6NC98Coiled-coil domain-containing protein 88B0.840.430.34 O00170AH receptor-interacting protein140.530.33 Q9Y2D2UDP-N-acetylglucosamine transporter0.44710.510.32 Q9Y285Phenylalanyl-tRNA synthetase alpha chain0.610.810.31 Q14683Structural maintenance of chromosomes protein 1A 130.840.35 Q16543Hsp90 co-chaperone Cdc370.82 20.32 Q15532Protein SSXT0.810.410.31 Q9NZR1Tropomodulin-20.510.31 1 P17213Bactericidal permeability-increasing protein0.91120.22 O95182NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 7 110.430.23 Q9BYX2TBC1 domain family member 2A0.920.310.21 Q92878DNA repair protein RAD500.820.620.21 O60879Protein diaphanous homolog 20.920.620.21 Q92922SWI/SNF complex subunit SMARCC10.920.610.21 Q9NR45Sialic acid synthase0.820.130.26 Q92614Myosin-XVIIIa120.810.23 P20674Cytochrome c oxidase subunit 5A, mitochondrial0.71 20.072 Q9H7M9Platelet receptor Gi240.810.210.032 Q8N8A2Serine/threonine-protein phosphatase 6 regulatory ankyrin repeat subunit B 0.83 10.031 O60826Coiled-coil domain-containing protein 220.910.0810.021 P22059Oxysterol-binding protein 10.810.310.011 Table S1

5. Table S2 PKC  of human monocytes becomes rapidly phosphorylated upon incubation with oxLDL Human monocytes were incubated for 5, 15 and 30 min. with 25  g of oxLDL, respectively. Cells were processed as described in “Methods” allowing semi-quantitative analysis of protein phosphorylation. Data expressed as relative to non-treated controls. Phosphorylated amino acid residues are depicted in green. Time point [min] Peptide(s) identifiedXCorrChargeMass TMT ratio 127/126Modification 5lLAEALNQVTQR3.352 1580. 9231.153N-Term(TMT2plex) 15 lLAEALNQVTQR3.653 1580. 920.765N-Term(TMT2plex) lLAEALNQVTQR3.543 1580. 922.103N-Term(TMT2plex), K3(TMT2plex) dLkLDNVLLDR3.183 1764. 0531.3N-Term(TMT2plex) lLAEALNQVTQR3.062 1580. 920.969N-Term(TMT2plex) aAEEPVSEVTVGV SVLAER2.833 2167. 168 carries only 127 labelN-Term(TMT2plex), K7(TMT2plex) vLLGELk2.722 1221. 8091.893N-Term(TMT2plex), K7(TMT2plex) 30 aTFYAAEIMcGLQF LHSk5.983 2537. 321.898 N-Term(TMT2plex), C10(Carbamidomethyl), K18(TMT2plex) aTFYAAEIMcGLQF LHSk53 2537. 3182.277 N-Term(TMT2plex), C10(Carbamidomethyl), K18(TMT2plex) aSTFcGTPDyIAPEI LQGLk3.363 2711. 37 carries only 127 label N-Term(TMT2plex), C5(Carbamidomethyl), Y10(Phospho), K20(TMT2plex) asTFcGTPDYIAPEI LQGLk3.253 2711. 37 carries only 127 label N-Term(TMT2plex), S2(Phospho), C5(Carbamidomethyl), K20(TMT2plex) aStFcGTPDYIAPEI LQGLk3.233 2711. 37 carries only 127 label N-Term(TMT2plex), T3(Phospho), C5(Carbamidomethyl), K20(TMT2plex) aSTFcGtPDYIAPEI LQGLk3.23 2711. 37 carries only 127 label N-Term(TMT2plex), C5(Carbamidomethyl), T7(Phospho), K20(TMT2plex) sTFDAHIYEGR3.033 1520. 7570.652N-Term(TMT2plex) lLAEALNQVTQR2.993 1580. 9192.093N-Term(TMT2plex) sTFDAHIYEGR2.873 1520. 7580.419N-Term(TMT2plex) vLLGELk2.722 1221. 811.917N-Term(TMT2plex), K7(TMT2plex)

6. Figure S2 Bone marrow-derived macrophages lacking NDK-A show normal uptake of oxLDL and cellular localization (A) BMDM obtained from NDK-A -/- mice were incubated with fluorescently labeled oxLDL for 3h (25  g/ml) and uptake was measured by flow cytometry. (B) Cellular localization of oxLDL (red) after 3h incubation with bone marrow-derived macrophages of NDK-A -/- mice was determined by confocal microscopy (LAMP-1 in green, nuclei in blue). wtNDK-A -/- A B

7. Figure S3 PKC inhibitor Gö6983 inhibits uptake of oxLDL. (A) Human monocyte-derived macrophages of healthy donors were treated 30 min prior to oxLDL addition with either rottlerin (10  M) or PKC inhibitor Gö6983 (10  M). Uptake of oxLDL was analyzed by flow cytometry and presented as percentage of uptake by non-treated cells. Data are presented as mean  SEM and are representative of 4 independent experiments (T-test, **p<0.01). (B) Human monocytes-derived macrophages of 4 healthy individuals and PKC  -/- patient V (■) and L1 (♦) were pretreated with PKC inhibitor Gö6983 (10  M) 30min prior to oxLDL. Uptake of oxLDL was analyzed by flow cytometry and presented as percentage of uptake by non-treated cells. A B CVR-2014-544

8. A Figure S4 Normal expression of CD36 in human monocytes/macrophages with reduced protein levels of PKC . (A) THP-1 cells transduced with shRNA targeting PKC  or (B) human monocytes with silenced expression of PKC  were analyzed for CD36 expression by flow cytometry. Data are presented as relative to controls treated with scramble shRNA (THP-1) or mock siRNA (human monocytes) and are representative of 3 (THP-1) and 4 (human monocytes) individual experiments. B CVR-2014-544