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.

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 A P22392Nucleoside diphosphate kinase B P50502Hsc70-interacting protein P28676Grancalcin Q kDa heat- and acid-stable phosphoprotein P25786Proteasome subunit alpha type P22234Multifunctional protein ADE Q01518Adenylyl cyclase-associated protein O60610Protein diaphanous homolog Q9BRF8Calcineurin-like phosphoesterase domain- containing protein P04114Apolipoprotein B P12956X-ray repair cross-complementing protein O60234Glia maturation factor gamma P07437Tubulin beta chain O14818Proteasome subunit alpha type Q9HDC9Adipocyte plasma membrane-associated protein P05141ADP/ATP translocase P06454Prothymosin alpha P22626Heterogeneous nuclear ribonucleoproteins A2/B P28066Proteasome subunit alpha type Q14152Eukaryotic translation initiation factor 3 subunit A P14625Endoplasmin P07237Protein disulfide-isomerase P35232Prohibitin Q99623Prohibitin O75533Splicing factor 3B subunit P12036Neurofilament heavy polypeptide P68366Tubulin alpha-4A chain Q14764Major vault protein Q6DD88Atlastin P31153S-adenosylmethionine synthase isoform type P protein gamma P05496ATP synthase lipid-binding protein, mitochondrial Q9H3G5Probable serine carboxypeptidase CPVL P53396ATP-citrate synthase P13010X-ray repair cross-complementing protein P S protease regulatory subunit Q13185Chromobox protein homolog

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 P11413Glucose-6-phosphate 1-dehydrogenase Q05655Protein kinase C delta type P26641Elongation factor 1-gamma O15143Actin-related protein 2/3 complex subunit 1B Q96D96Voltage-gated hydrogen channel P31948Stress-induced-phosphoprotein P07910Heterogeneous nuclear ribonucleoproteins C1/C O75351Vacuolar protein sorting-associated protein 4B P S protease regulatory subunit P08107Heat shock 70 kDa protein 1A/1B Q92688Acidic leucine-rich nuclear phosphoprotein 32 family member B P13796Plastin Q02750Dual specificity mitogen-activated protein kinase kinase P60842Eukaryotic initiation factor 4A-I P S protease regulatory subunit 6A P52565Rho GDP-dissociation inhibitor P60709Actin, cytoplasmic O S proteasome non-ATPase regulatory subunit P13667Protein disulfide-isomerase A P50570Dynamin P54136Arginyl-tRNA synthetase, cytoplasmic P31689DnaJ homolog subfamily A member P54577Tyrosyl-tRNA synthetase, cytoplasmic O75582Ribosomal protein S6 kinase alpha Q8N684Cleavage and polyadenylation specificity factor subunit Q8ND76Cyclin-Y P63241Eukaryotic translation initiation factor 5A O14773Tripeptidyl-peptidase Q96L92Sorting nexin P32119Peroxiredoxin Q07065Cytoskeleton-associated protein Q13464Rho-associated protein kinase P62318Small nuclear ribonucleoprotein Sm D Q7L591Docking protein O14745Na(+)/H(+) exchange regulatory cofactor NHE-RF P04083Annexin A

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 Q8NBS9Thioredoxin domain-containing protein P37108Signal recognition particle 14 kDa protein A6NC98Coiled-coil domain-containing protein 88B O00170AH receptor-interacting protein Q9Y2D2UDP-N-acetylglucosamine transporter Q9Y285Phenylalanyl-tRNA synthetase alpha chain Q14683Structural maintenance of chromosomes protein 1A Q16543Hsp90 co-chaperone Cdc Q15532Protein SSXT Q9NZR1Tropomodulin P17213Bactericidal permeability-increasing protein O95182NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit Q9BYX2TBC1 domain family member 2A Q92878DNA repair protein RAD O60879Protein diaphanous homolog Q92922SWI/SNF complex subunit SMARCC Q9NR45Sialic acid synthase Q92614Myosin-XVIIIa P20674Cytochrome c oxidase subunit 5A, mitochondrial Q9H7M9Platelet receptor Gi Q8N8A2Serine/threonine-protein phosphatase 6 regulatory ankyrin repeat subunit B O60826Coiled-coil domain-containing protein P22059Oxysterol-binding protein Table S1

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 5lLAEALNQVTQR N-Term(TMT2plex) 15 lLAEALNQVTQR N-Term(TMT2plex) lLAEALNQVTQR N-Term(TMT2plex), K3(TMT2plex) dLkLDNVLLDR N-Term(TMT2plex) lLAEALNQVTQR N-Term(TMT2plex) aAEEPVSEVTVGV SVLAER carries only 127 labelN-Term(TMT2plex), K7(TMT2plex) vLLGELk N-Term(TMT2plex), K7(TMT2plex) 30 aTFYAAEIMcGLQF LHSk N-Term(TMT2plex), C10(Carbamidomethyl), K18(TMT2plex) aTFYAAEIMcGLQF LHSk N-Term(TMT2plex), C10(Carbamidomethyl), K18(TMT2plex) aSTFcGTPDyIAPEI LQGLk carries only 127 label N-Term(TMT2plex), C5(Carbamidomethyl), Y10(Phospho), K20(TMT2plex) asTFcGTPDYIAPEI LQGLk carries only 127 label N-Term(TMT2plex), S2(Phospho), C5(Carbamidomethyl), K20(TMT2plex) aStFcGTPDYIAPEI LQGLk carries only 127 label N-Term(TMT2plex), T3(Phospho), C5(Carbamidomethyl), K20(TMT2plex) aSTFcGtPDYIAPEI LQGLk carries only 127 label N-Term(TMT2plex), C5(Carbamidomethyl), T7(Phospho), K20(TMT2plex) sTFDAHIYEGR N-Term(TMT2plex) lLAEALNQVTQR N-Term(TMT2plex) sTFDAHIYEGR N-Term(TMT2plex) vLLGELk N-Term(TMT2plex), K7(TMT2plex)

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

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

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