PRPF4B PRPF4B RET MAP2K1 CDK3 MAPK1 SRC ABL1 CDK2 PTK2 LYN CDK1 MAPK3 JAK2 TTK MAPK1 DYRK1B MAP2K1 EGFR PTK2 DYRK1A PKMYT1 ERBB2 MAPK3 MAPK14 ERBB2 FGR TNK2 YES1 BMX KDR DYRK1B SRC MET MAP2K2 DYRK1A FYN PTK2 YES1 MAPK14 MAPK9 FGR INSR YES1 MAPK3 MAP2K3 FYN INSR MAP2K2 MAPK3 PEAK1 IGF1R ABL1 MAP2K6 SRC HIPK2 MAP2K4 FYN SYK HIPK1 MAP2K6 KIT MAPK9 GSK3B MAP3K6 ITK LCK SKMel28.Replicate.1 GSK3A SKMel28.Replicate.1 MAP3K5 SKMel28.Replicate.1 SRMS SKMel28.Replicate.1 AXL Kinome DYRK4 ActLoop CDK5 PSP MET NWK CDK16 DYRK2 ALK MAP2K4

0 10 20 30 40 50 0 10 20 30 40 50 0 20 40 60 80 100 0 10 20 30 40 50 60 70

Not in PSP/NWK INKA SKMel28.Replicate.1 PEAK1 1 MAPK3 ● 36 AXL SRC ● DYRK4 PTK2 ● CDK17 0.9 33 HIPK3 0.8 29

0.7 25

0.6 22 Score 0.5 18 YES1 ● JAK2 ● FYN ● Relative Score Relative 0.4 15 ● INSR ● MAPK14 LYN ● 0.3 11 MAPK1 ● LCK ●IGF1R ● 0.2 ● HIPK2 FGR ● 7 CDK1 CDK5 ● GSK3A ● GSK3B TYK2 ● 0.1 TNK2 ● EPHA2 ● FER ● 4 SYK ● ● HCK ● ALPK3 MAPK10 ● EPHA3 ABL2 ● AKT1 0 2 4 6 −CentricAKT2 ● AKT3 Equal Substrate−CentricABL1 ● ADRBK1 EvidenceARAF Only Contribution EvidenceALK Only Kinase−Centric Counts

InKA Score SKMel28.Replicate.1

MAPK3 SRC PTK2 YES1 JAK2 FYN INSR MAPK14 LYN MAPK1 LCK IGF1R FGR CDK1 CDK5 GSK3A GSK3B HIPK2 TYK2 EPHA2

0 5 10 15 20 25 30 35 SKMel28.Replicate.1

FYN LCK

CAV1 TYK2 IGF1R ITK GSK3A

TEC

YES1 STAT3

GSK3B PEAK1 CDK2 INSR VCL JAK2

MAP2K4 MAP2K1

PKMYT1 LYN

TTK MAPK1

PTPRA MAP3K5 MAP3K6

MAPK3 WEE1 PRKACA

MPZL1 MAPK14 MAP2K6 CDK1

RET HIPK2 MAP2K2 SRC

PDGFRB PXN

PDGFRA ABL1 MAP2K3 MET BMX EGFR

FGR ERBB2 KDR PTK2

CDK5 CDK3 PRPF4B WEE1 ABL1 CDK2 MAPK1 SRC MAP2K1 CDK1 GSK3B RET LYN PRPF4B GSK3A MAP2K1 TTK MAPK1 PTK2 JAK2 EGFR PTK2 MAPK3 PKMYT1 ERBB2 GSK3B DYRK1B ERBB2 FGR GSK3A DYRK1A BMX MAP2K2 MAPK3 MAPK14 MET KDR DYRK1B HIPK2 PTK2 INSR DYRK1A HIPK1 GSK3B YES1 MAPK14 YES1 GSK3A MAP2K3 YES1 SRC MAPK3 FYN FYN LCK MAP2K2 MAPK3 TNK2 FYN FGR KIT HIPK2 INSR ABL1 MAP2K6 HIPK1 IGF1R MAP2K6 SRMS PEAK1 SKMel28.Replicate.2 DYRK4 SKMel28.Replicate.2 MAP2K4 SKMel28.Replicate.2 ITK SKMel28.Replicate.2 LCK Kinome DYRK2 ActLoop ALK PSP MET NWK AXL AXL CDK5 PDGFRA

0 10 20 30 40 50 0 10 20 30 40 50 0 20 40 60 80 100 0 20 40 60

Not in PSP/NWK INKA SKMel28.Replicate.2 AXL 1 SRC ● 33 DYRK4 PEAK1 ● CDK17 0.9 MAPK3 30 HIPK3 0.8 26 GSK3APTK2 ●● GSK3B 0.7 23

0.6 20 Score 0.5 16 ● Relative Score Relative YES1FYN● 0.4 MAPK1 ● INSR ● 13 ● MAPK14 JAK2 ● 0.3 LCK ● 10 HIPK2 ● IGF1R ● LYN ● 0.2 CDK5 ● FGR ● 7 EPHA2 ● TYK2 ● 0.1 3 ABL2 ● AKT2 EPHA3MAPK10● ● BCR−ABL 0 2 4 6 ADRBK1Kinase−Centric● AKT1 Equal Substrate−CentricABL1 ● ALK EvidenceAKT3 Only Contribution EvidenceBMX Only Kinase−Centric Counts

InKA Score SKMel28.Replicate.2

SRC MAPK3 PTK2 GSK3A GSK3B FYN YES1 INSR MAPK1 MAPK14 JAK2 LCK HIPK2 IGF1R LYN FGR CDK5 EPHA2 TYK2 ABL2

0 5 10 15 20 25 30 SKMel28.Replicate.2

GSK3A

PEAK1

LCK LYN CDK2

PDGFRB CDK1 TYK2 ITK

HIPK2 PRKACA IGF1R INSR PTPRA YES1

SRC PDGFRA FYN VCL KDR MAP2K4

EPHA2 EGFR MAP2K6 MAP3K6

BCAR1 MET

MAP3K5 PTK2 MAP2K3 GSK3B MAPK14 SYK

BMX MAP2K2

FGR ABL1 RET MAP2K1 MAPK3

ERBB2

STAT3 JAK2

PXN CDK5 MAPK1 ALK PTK2 SRC EGFR CDK1 MAPK14 RET ERBB2 CDK3 PRPF4B WEE1 MET CDK2 GSK3B MET INSR PTK2 GSK3A BMX ABL1 MAPK14 MAPK3 PKMYT1 LYN PRPF4B DYRK1B ERBB2 EPHA1 GSK3B DYRK1A PTK2 TTK GSK3A MAPK1 MAP2K1 MAP2K1 LYN YES1 ALK YES1 EPHA2 SRC FGR KDR MAPK3 LCK JAK2 FGR DYRK1B FYN EGFR FYN DYRK1A EPHA2 ABL1 KIT TNK2 HIPK2 MAP2K4 EPHA2 PEAK1 HIPK1 INSR ITK MAPK1 LYN MAP3K6 MAP2K6 YES1 H2228.Replicate.1 HCK H2228.Replicate.1 MAP3K5 H2228.Replicate.1 MAP2K7 H2228.Replicate.1 FYN Kinome INSR ActLoop MAP2K6 PSP MAPK3 NWK AXL IGF1R MAP2K3 FLT1

0 10 20 30 40 50 60 0 5 10 15 20 25 30 35 0 50 100 150 200 0 50 100 150

Not in PSP/NWK INKA H2228.Replicate.1 PEAK1 1 PTK2 ● 58 AXL DYRK4 SRC ● HIPK3 0.9 52 CDK17 ALK ● 0.8 46

0.7 40 LYN ● 0.6 MET ● 35 EGFR ●

MAPK3 EPHA2● ● Score 0.5 INSR ● 29 FYN ● ABL1 ●

Relative Score Relative YES1 ● MAPK14 ●GSK3A ● GSK3B 0.4 23

0.3 17 LCK ● MAPK1 ●

ABL2 ● ● 0.2 HCK ● IGF1R 12 JAK2FGR● ● CDK1CDK2 ● HIPK2 ● TYK2 ● 0.1 FGFR1 FERCDK5● ● 6 EPHA3 ● AURKA EPHA4 ● EPHB4 EPHB3 ● AKT2 MAPK10 ● TGFBR2SYK ● 0 2 4 6 8 10 ALPK3Kinase−Centric● ARAF Equal ADRBK1Substrate−Centric● AKT1 EvidenceAURKB Only Contribution EvidenceAKT3 Only Kinase−Centric Counts

InKA Score H2228.Replicate.1

PTK2 SRC ALK LYN MET EGFR EPHA2 MAPK3 INSR ABL1 FYN YES1 MAPK14 GSK3A GSK3B LCK MAPK1 ABL2 IGF1R HCK

0 10 20 30 40 50 H2228.Replicate.1

MAP3K5 MAP2K2 MAP2K3

DOCK4 JAK2 MAP2K6

GSK3A MAP2K1

EPHA2 GSK3B MAP2K4 MAPK3 MAPK14 TEC CDK2 MAPK1

MAP3K6 EPHA1 ITGB1 PEAK1 GAB2 EML4 PXN

ABI1 RET

INPPL1 ALK CTNNA1 VASP GPRC5A KDR HCK ABL2 LYN MST1R STAT3 FGR PTPN11 MAP2K7 CRK ABL1 BMX NCK1 EGFR KIT ITGB4 PRKCE INPP5D PTK2 MET CDK1

CTNNA2 MPZL1 BCAR1 ACTN1 ERBB2 TNK2 CBL GAB1 CAV1 CTNND1 VCL MUC1 CTTN LCK YES1

SHC1 PTPRE FYN SRC PAG1 INSR ITK IRS1

PTPRA IGF1R PDGFRA CD46 PDGFRB G6PD PIK3R1 NAMPT HIPK2 SDCBP PFN1 IRS2 AP2B1 PIK3R3 PRKACA PTTG1IP PRPF4B PRPF4B SRC EGFR CDK1 PTK2 WEE1 MET ALK MAPK14 RET ERBB2 CDK3 GSK3B MET ABL1 CDK2 GSK3A PKMYT1 INSR PTK2 MAPK3 ERBB2 LYN MAPK14 MAPK1 ALK TTK LYN DYRK1B BMX EPHA1 GSK3B DYRK1A JAK2 YES1 GSK3A EPHA2 MAP2K1 MAP2K1 TNK2 YES1 ABL1 FGR MAPK3 SRC PTK2 FYN MAPK1 LYN EGFR KDR DYRK1B LCK FGR KIT DYRK1A HIPK2 MAP2K4 ITK YES1 HIPK1 FYN TEC FYN HCK MAP3K5 MAPK3 EPHA2 H2228.Replicate.2 FYN H2228.Replicate.2 MAP2K6 H2228.Replicate.2 EPHA2 H2228.Replicate.2 HCK Kinome ABL2 ActLoop MAP2K3 PSP TYK2 NWK EGFR ABL1 INSR MAP2K7

0 10 20 30 40 50 0 10 20 30 40 50 0 50 100 150 200 0 50 100 150

Not in PSP/NWK INKA H2228.Replicate.2 PEAK1 1 SRC ● 50 AXL DYRK4 ALK ● PTK2 ● HIPK3 0.9 45

CDK17 ● 0.8 LYN 40

● 0.7 EGFRMET ● 35

0.6 ABL1 ● 30 ● YES1FYN ●

MAPK3 ● Score 0.5 25 GSK3A ● GSK3B Relative Score Relative MAPK14 ● EPHA2 ● 0.4 20

0.3 INSR ● 15 MAPK1 ● HCK ● LCK ERBB2 ● ABL2 ● JAK2 ● 0.2 CDK1CDK2 ● 10 ● HIPK2 TYK2 ●FGR ● EPHB4 ● CDK5 ● 0.1 EPHB3 ● IGF1R ● 5 TNK2 ● ERBB4 ● AURKA AKT2 FRK ● 0 1 2 3 4 5 ALPK3Kinase−Centric● ARAF Equal ADRBK1Substrate−Centric● AKT1 EvidenceAURKB Only Contribution EvidenceAKT3 Only Kinase−Centric Counts

InKA Score H2228.Replicate.2

SRC ALK PTK2 LYN EGFR MET ABL1 FYN YES1 MAPK3 GSK3A GSK3B EPHA2 MAPK14 INSR HCK LCK MAPK1 ERBB2 ABL2

0 10 20 30 40 H2228.Replicate.2

PIK3R3 IRS1 PIK3R1 KIT ITGB1 NAMPT

TEC NCK1 IRS2 CDK2 ABL2

MAP2K1 ITK INSR JAK2

GSK3B LYN HCK LCK FYN PTPRA MAPK3 ABL1 PXN INPP5D MAP2K2

PAG1 BCAR1 MAP2K3 MPZL1 MAPK1

PDGFRB GAB2 FGR CTNND1 CAV1 MAPK14 MAP3K6 PTTG1IP GAB1 RET HIPK2 INPPL1 CDK1 EPHA2 MAP3K5 G6PD SRC PRKACA MET MAP2K4 CTTN BMX MST1R ADRBK1 PTK2 PDGFRA EGFR MAP2K6 AP2B1 SHC1 MUC1 CBL PRKCE ITGB4

SDCBP GSK3A CD46 CAMK2A EML4 ERBB2 KDR PTPN11

GPRC5A EPHA1 YES1 TNK2 STAT3 VCL ALK HSP90AA1

TNS3 VIM ACTN1 ARHGAP35 HSP90AA2P MAP2K7 PTPRE BCR PRPF4B SRC ABL1 ABL1 MAPK1 WEE1 MET CDK1 ABL1 LYN ABL2 CDK3 ABL2 FYN LYN CDK2 MAPK14 HCK BTK PRPF4B DYRK1B ABL1 TTK ABL2 DYRK1A PKMYT1 EGFR MAPK1 MAPK3 ERBB2 KIT MAPK14 GSK3B BCR−ABL NTRK1 PEAK1 GSK3A RET MAP2K1 LYN YES1 JAK2 ERBB2 DYRK1B SRC MAP2K1 TYK2 DYRK1A FYN LCK PDGFRB MAPK3 HIPK2 MET TEC BTK HIPK1 SYK FLT1 TNK2 LYN ABL2 ITK GSK3B LCK ALK INSR GSK3A K562.Replicate.1 HCK K562.Replicate.1 MAPK3 K562.Replicate.1 MAPK1 K562.Replicate.1 YES1 Kinome DDR1 ActLoop MAP3K5 PSP YES1 NWK FYN HIPK3 MAP2K4 FGR

0 50 100 150 0 10 20 30 40 50 60 0 50 100 150 200 250 0 50 100 150 200

Not in PSP/NWK INKA K562.Replicate.1 PEAK1 1 ABL1 ● 273 DDR1 HIPK3 CDK17 0.9 245 DYRK4 AXL 0.8 218 FAM20B 0.7 191

0.6 164 Score 0.5 136 ABL2 ● Relative Score Relative 0.4 109 LYN ● 0.3 82 SRC ● MAPK1 ● FYN ● 0.2 BTK ● 55 MAPK3 ● HCK ●

0.1 YES1 ● LCK ● 27 GSK3A ● GSK3B JAK2 ● CDK1CDK2AKT3● ● TNK2 ● BCR−ABL MAPK14 HIPK2 ● SYK ● ●● PTK2 ● ● ●BMXTYK2FGRTEC● 0 5 10 15 20 ADRBK1Kinase−Centric● AKT2 EPHB4 ● MAPK10AURKAEqual● CDK5 PRKCB Substrate−CentricAKT1 ● ALK EvidenceALPK3 Only Contribution EvidenceBLK Only Kinase−Centric Counts

InKA Score K562.Replicate.1

ABL1 ABL2 LYN SRC FYN MAPK1 BTK MAPK3 HCK YES1 LCK GSK3A GSK3B JAK2 TNK2 CDK1 CDK2 MAPK14 HIPK2 SYK

0 50 100 150 200 250 K562.Replicate.1

ARHGAP35

PRKACA CD46 YES1 ACTN1

CTTN GSK3A GAB1 PTPRA

PTTG1IP G6PD MAP2K3 PFN1 MAP3K6 SHC1 MAP3K5 PTK2 PDGFRA HIPK2 ERBB2 SRC PKMYT1 MAPK14 MAP2K6 PDGFRB EGFR FGR STAT5B MPZL1 TTK MAP2K4 BMX WEE1

ABL2 CDK1 PRKCD NTRK1 HCK GSK3B CDK2 RET CRK TNK2 PEAK1

STAT5A ABL1 INPPL1

ABI1 KIT MAPK1 LYN DOK1

BCR JAK2 MAP2K1 NTRK2 WAS

MAPK3 GAB2 NCK1 PLCG1 BTK SYK TEC FYN LCK

MAP2K2 DOK2 FCGR2A FCGR2C

FYB ITK

CBL PIK3R2 SH2D2A BCR PRPF4B SRC ABL1 ABL1 ABL1 WEE1 MET CDK1 MAPK1 LYN ABL2 CDK3 ABL2 FYN LYN CDK2 MAPK14 HCK BTK PRPF4B MAPK3 ABL1 TTK ABL2 GSK3B PKMYT1 KIT MAPK1 GSK3A ERBB2 EGFR MAPK14 DYRK1B BCR−ABL NTRK1 LYN DYRK1A RET MAP2K1 BTK YES1 JAK2 ERBB2 MAPK3 SRC MAP2K1 TYK2 GSK3A FYN LCK ITK PEAK1 HIPK2 MET TEC GSK3B HIPK1 ABL2 FLT1 DYRK1B LYN ALK YES1 DYRK1A LCK SYK FGR YES1 K562.Replicate.2 HCK K562.Replicate.2 MAPK3 K562.Replicate.2 MAPK1 K562.Replicate.2 TNK2 Kinome PTK2 ActLoop EGFR PSP INSR NWK FYN DDR1 MAP2K4 PDGFRB

0 50 100 150 0 10 20 30 40 50 0 50 100 150 200 250 0 50 100 150 200

Not in PSP/NWK INKA K562.Replicate.2 PEAK1 1 ABL1 ● 269 DDR1 HIPK3 CDK17 0.9 242 DYRK4 AXL 0.8 215 TRIM28 0.7 188

0.6 161 Score 0.5 ABL2 ● 135 Relative Score Relative 0.4 108 LYN ● 0.3 81 FYNSRC● ● 0.2 MAPK1 ● BTK ● 54 MAPK3 ● HCK ● ● 0.1 ● YES1 ● 27 CDK1CDK2 GSK3AGSK3B ●● LCK JAK2 ● AKT3 ● TECTTKBCR−ABL● ● ● HIPK2● ●TNK2 SYKFGR ●●● MAPK14 ● PTK2 ● ● CDK5 ● ● TYK2 0 5 10 15 ADRBK1Kinase−CentricPRKCD● AKT2 MAPK10EPHB4 ● AURKAFEREqual● PRKCB Substrate−CentricAKT1 ● ALK EvidenceALPK3 Only Contribution EvidenceBLK Only Kinase−Centric Counts

InKA Score K562.Replicate.2

ABL1 ABL2 LYN FYN SRC BTK MAPK1 HCK MAPK3 YES1 CDK1 CDK2 LCK GSK3A GSK3B JAK2 TEC TTK TNK2 FGR

0 50 100 150 200 250 K562.Replicate.2

DOK1

FCGR2C KIT CBL

ITK DOK2 PEAK1

ABI1 SH2D2A FYN NCK1 TEC

FCGR2A LCK BTK NTRK2 BMX BCR

MAP2K2 CRK LYN JAK2

ABL2 WAS GAB2

ABL1

MAPK3 PLCG1 TNK2 RET ARHGAP35 HCK STAT5A

MPZL1 MAPK1 NTRK1 CDK2 PRKCD GSK3A INPPL1

FGR CDK1 WEE1

YES1 SHC1 STAT5B MAP2K1 EGFR

SRC PKMYT1 PPP1CA CD46 ACTN1 TTK PTPRA PTK2 GSK3B

ERBB2

PRKACA CTTN PDGFRB PDGFRA HIPK2

CDK3

GAB1 PTTG1IP G6PD MET MET SRC MET EGFR GSK3B MET EGFR NRK GSK3A ABL1 ERBB2 EPHA2 PTK2 MST1R EPHA2 PEAK1 EPHA2 EGFR PRKCE CDK1 EGFR BMX FYN PTK2 MST1R LYN YES1 FRK TYRO3 FYN MAPK3 CDK3 PRPF4B WEE1 ABL1 CDK2 MERTK RET INSR MINK1 JAK1 EPHA2 EPHB2 ROR1 HIPK2 INSR TYK2 GSK3B HIPK1 PKMYT1 EPHB4 GSK3A EPHB4 ERBB2 EPHB1 TNK2 DYRK1B LCK ERBB4 AXL DYRK1A ALK ITK EPHB4 MAPK14 PTK2 EPHA4 YES1 HCC827ER3.Replicate.1 MAPK12 HCC827ER3.Replicate.1 MAP2K1 HCC827ER3.Replicate.1 LYN HCC827ER3.Replicate.1 LYN Kinome MAPK1 ActLoop GSK3B PSP ADRBK1 NWK FYN AXL FGR ERBB3

0 50 100 150 200 0 20 40 60 80 0 50 100 150 200 250 300 350 0 100 200 300 400

Not in PSP/NWK INKA HCC827ER3.Replicate.1 PEAK1 1 MET ● 467 AXL ROR1 TYRO3 0.9 421 DYRK4 GAK 0.8 374 ALPK3 BMP2K 0.7 327 BMPR2 0.6 EGFR ● 280 Score 0.5 234 Relative Score Relative 0.4 187

0.3 140

0.2 EPHA2 ● 93

ERBB2● ● 0.1 MST1RFYNSRC● ● 47 PTK2 ● ● EPHB4YES1● LYNABL1● ● ● GSK3A GSK3B● ●● ALPK3 FRK ERBB4EPHB2●MAPK3● ● ALK CDK1 ●● MAPK1●ERBB3EPHA4LCK●●●● CDK2 JAK1HIPK2●●MELKMERTK● MAPK14CDC42BPB● ● ● EPHA5EPHA3● ABL2●● JAK2HCKEPHB3PRKCAPRKCITTK●●TYK2●FGR●●● 0 10 20 30 Kinase−CentricAKT2 ● AKT3 TGFBR2MAPK10 CSNK1A1Equal● FER LMTK2CDK5ADRBK1Substrate−Centric● AKT1 EvidenceARAF Only Contribution EvidenceAURKA Only Kinase−Centric Counts

InKA Score HCC827ER3.Replicate.1

MET EGFR EPHA2 ERBB2 MST1R SRC FYN ABL1 EPHB4 YES1 PTK2 LYN GSK3A GSK3B MAPK3 EPHB2 FRK ERBB4 MAPK1 LCK

0 100 200 300 400 HCC827ER3.Replicate.1

TP53BP2 CBLB ITGB5 ACTN1 TYRO3

CHN2 OCLN LAT2 PEAK1 VCL YES1 PPP1R9A TEC

CDK2 ITK LCK DLG1 CDK4 PIK3R2 KIT PAG1 ARHGAP35 YAP1 CD46 PTPN6 PFN1 ACP1 ZDHHC8 HIPK2 ERBB4 FYN BCR ABI2 LYN PRKCD MPZL1 FRK STK11 G6PD APP PBK CBL GIT1 EMD

ITCH STAM2 PTTG1IP EPN2 CAV1 PTPRA EPHA2 BCAR1 SRC ARHGAP5

ITGB4 ABL1 RGS3 CTNND1 CCDC88A CRK CRKL KDR PLCG1 GJA1 ADRBK1 EFNB2 SPRY2 MST1R MET SHC1 CDK1 SDCBP

BMX EPHB4 PTK2 STAT1 CTTN PRKCE STAM PXN EGFR EPS8 EPHB2 FGR GAB1 INPPL1 GPRC5A PTPN11 PDGFRB ABI1 TNK2 ERRFI1 EFNB1

GAB2 RAB5A EPB41 RAC1 MAPK3 TJP1 RET MAP2K1 ERBB2 PKM CAMK2A WASL JAK2 MAPK1 TTK USP6NL DAG1 VIM ERBB3 IRS2 HLA−A GSK3B RIPK1 LRP6 TNS3 ERBB2IP*

MAP2K2 COPS5 GSK3A OSMR MET MET SRC MET EGFR PTK2 MET EGFR NRK GSK3B ABL1 ERBB2 EPHA2 GSK3A MST1R FYN PTK2 EPHA2 BMX PRKCE PEAK1 EGFR EGFR EPHA2 CDK1 MST1R FYN MAPK3 CDK3 PRPF4B RET ABL1 CDK2 MAPK8 WEE1 INSR FRK MAPK3 LYN YES1 TNK2 MAPK10 EPHA2 EPHB2 ROR1 MAPK1 INSR TYK2 MINK1 JAK1 PTK2 ITK GSK3B HIPK2 FGR EPHB4 GSK3A HIPK1 PKMYT1 ERBB4 AXL EPHB4 ERBB2 EPHB1 EPHB4 DYRK1B LCK LYN EPHB2 HCC827ER3.Replicate.2 DYRK1A HCC827ER3.Replicate.2 ALK HCC827ER3.Replicate.2 EPHA4 HCC827ER3.Replicate.2 PRKCD Kinome AXL ActLoop MAP2K1 PSP ADRBK1 NWK LYN MAPK12 JAK2 TTK

0 50 100 150 200 0 20 40 60 80 100 0 100 200 300 0 100 200 300 400 500

Not in PSP/NWK INKA HCC827ER3.Replicate.2 PEAK1 1 MET ● 495 AXL ROR1 TYRO3 0.9 445 DYRK4 GAK 0.8 396 BMPR2 PKN2 0.7 346 ALPK3 EGFR ● BMP2K 0.6 297 FAM20B Score 0.5 247 Relative Score Relative 0.4 198

0.3 148

0.2 EPHA2 ● 99

PTK2 ● MST1RERBB2● ● 0.1 ● 49 ● LYN●FYNSRC● ● ● EPHB4EPHB2MAPK3YES1 ● ALPK3 GSK3A GSK3BFRK ● ● ERBB4ABL1● ALK● ●● MAPK1 EPHA4EPHB1TYK2LCK●●●●● CDK2CDK1 MERTKJAK1 ● HIPK2● ● MAPK10CDC42BPB●MAPK14● ● EPHA3ABL2●ERBB3●EPHB3EPHA5JAK2PRKCA●PRKCITTK●FGR●●●● 0 10 20 30 Kinase−CentricAKT2 ● AKT3 CSNK1A1TGFBR2 ● MELK EqualLMTK2 ● FERHCKCDK5ADRBK1Substrate−Centric● AKT1 EvidenceARAF Only Contribution EvidenceAURKA Only Kinase−Centric Counts

InKA Score HCC827ER3.Replicate.2

MET EGFR EPHA2 MST1R ERBB2 PTK2 SRC FYN LYN EPHB2 EPHB4 MAPK3 YES1 GSK3A GSK3B ABL1 FRK ERBB4 MAPK1 LCK

0 100 200 300 400 HCC827ER3.Replicate.2

GSK3A VCL ACTN1 ERBB2IP* TYRO3 ERBB3 RIPK1 CBLB COPS5 OCLN HLA−A TNS3 ITGB5 HSP90AA2P YES1 VIM

STK11 OSMR RASA1 GIT1 EPHB4 ARHGAP35 HSP90AA1 CD46 PTPRA

HIPK2 ERBB2 FRK ARHGAP5 TTK CHN2 ACP1 SPRY2 FGR SDCBP EPB41 EFNB2 PKM PTTG1IP YAP1 PFN1 STAT1 EPHA2 JUP ADRBK1 CAMK2A

RAC1 G6PD CDK1 USP6NL CCDC88A SRC CTTN LCK SHC1 KDR STAT3 EPS8 EPHB2 GJA1 EMD PTPN6 PTK2 EGFR TJP1 PLCG1 GPRC5A TEC PBK PAG1 CAV1 NOTCH1 EFNB1 HGS PRKCD ABL1 CTNND1 TNK2 INPPL1 GAB1 ERRFI1 MPZL1 WASL SGK223* LYN CBL BMX ABI1 RAB5A MET STAM ABI2 RET CDK2 ITCH BCR FYN BCAR1

ITGB4 MAP2K1 PTPN11 PEAK1 MAPK3 DLG3 APP PXN MAPK1

LAT2 GAB2 MST1R HSP90AB3P ERBB4 PRKCE JAK2 KIT EPN2 GSK3B CRKL DLG1

PIK3R2 ITK MAP2K2 IRS2 DAG1