mRNA expression Name - Level -Tissue ALL Ant-FGFR2 FGFR4 HC High The Cancer Kinome antibody AXL LNM FGFR3 HC EphA5 he phylogenetic tree illustrates the similarity between the TK EphA3 T AP7637b BTK BLD sequences of the catalytic domains of the superfamily of 518 human EphA4 EphB2

JAK1 BLD EphB1 Yes HCK Src Lyn TRKB protein kinases. The seven major groups are colored separately. TK - TRKA FLT4 APL EphA6

Lck MuSK SYK BLD TRKC Tyrosine kinase; TKL - Tyrosine kinase–like; STE - Homologs of yeast Sterile EphB3 DDR2 Fyn EphA7 SRC ALL DDR1 7, Sterile 11, Sterile 20 kinases; CK1 - Casein kinase 1; AGC - Containing BLK TEC JAK3 ALL Etk/BMX TXK IGF1R Fgr InsR EphB4 FGFR2 FGFR3 Axl FGFR1 PKA, PKG, PKC families; CAMK Calcium/calmodulin-dependent protein JAK2 APL BTK ITK IRR ROR2 EphA8 Mer ROR1

KDR APL CTK EphA2 LTK Tyro3/Sky Alk Ros kinase; CMGC - Containing CDK, MAPK, GSK3, CLK families. 187 CSK Ron FGFR4 FLT1 Arg KDR FES APL Abl FRK Met Srm EphA1 Ret Brk protein kinases were found to be specific for variety of malignant tissues FLT4 Fms/CSFR FGFR2 APL Kit Fes FLT3 Fer EphB6 EGFR HER2 HCK APL RYK and are labeled in black. The inset diagram on the left shows the mRNA EphA10 PDGFa FAK PDGFRb FLT1 APL PYK2 Syk HER4 ZAP70 Ack level of expression for 20 protein tyrosine kinases in six different malignant TIE2 INSR APL TIE1 Tnk1 HER3 Tyk2 TIE BLR JAK1 tissues. JAK2 JAK3~b JAK3 JAK1~b Lmr1 ALK BLD Tyk2~bJAK~b Lmr2 HSERANPb SuRTK106 ANPa HeLa Low EGFR HC CCK4/PTK7 IRAK4 Lmr3 IRAK2 IRAK3 TKL CYGFCYGD IRAK1 Tissue type RIPK1 RIPK3 Acute Lymphoblastic Leukemia ...... ALL. . . ANKRD3 RIPK3 SgK288 Acute Promyelocytic Leukemia ...... APL . . . LRRK1 LRRK2 Burkitt's Lymphoma Daudi ...... BLD . . . . . LIMK1 LIMK2 MOS Burkitt's Lymphoma Ramos ...... BLR . . . . . MLKL TESK1 SgK496 TESK2 Hepatocellular carcinoma...... HC...... PBK ZAK MLK2 MLK3 Lymph node melanoma ...... LNM ...... MLK1 ILK MLK4 TAK1 DLK HH498 LZK KSR KSR2 BRAF ARAF RAF1 SgK307 KSR SgK424 ARAF KSR KSR ARAF KSR KSR KSR KSR PERK/PEK NRBP2 TGFbR2 DYRK4 MISR2 NRBP1 DYRK2 PKR BMPR2 DYRK3 PRP4 DYRK1A WNK4 DYRK1B GCN2

IRE1 WNK3 SgK071 HIPK4 TTK IRE2 CLIK1L HIPK3 CLIK1 WNK1 KIS HIPK1 RNAseL WNK2 HIPK2 CLK4 HRI NIK TBCK CLK1 COT CLK2 STE CLK3 MEKK1/MAP3K1 MSSK1 Ck2a1 SRPK2 Ck2a2 MAP3K8 SRPK1 CDC7 MEKK2/MAP3K2 MAK MAP3K4 ICK MEKK3/MAP3K3 MOK GSK3b ASK/MAP3K5 GSK3a CDKL3 SCYL1 HPK1 CDKL2 SCYL3 CDKL1 SgK196 KHS1 SCYL2 PRPK CDKL4 Hadpin MAP3K7 KHS2 CDLK5 SgK269 PINK1 SgK493 MEKK6/MAP3K6 GCK ERK4 IKKa SgK223 SgK396 IKKb Slob MST1 ERK3 PIK3R4 NLK IKKe OSR1 MST2 ERK5 TBK1 Bub1 STLK3 ERK7 BubR1 YSK1 ERK1 SgK069 MST3 CMGC ERK2 SgK110 STLK6 SBC p38g STLK5 MST4 MPSK1 p38d AAK1 HGK/ZC1 p38b BIKE p38a CAMKK1 GAK TLK2 SLK MINK/ZC3 CDK4 TLK1 CAMKK2 LOK CDK6 JNK1 ULK3 TNIK/ZC2 JNK3 ULK1 PLK4 TAO1 NRK/ZC4 PFTAIRE2 JNK2 ULK2 VRK3 TAO2 PFTAIRE1 PITSLRE Nek6 Fused TAO3 PAK1 PCTAIRE2 CDK10 Nek7 ULK4 CDK7 PAK3 PCTAIRE1 Nek2 PCTAIRE3 CK1g2 PAK2 Nek11 PLK1 CDK3 PAK4 Nek4 TTBK1 CDK2 TTBK2 Nek3 PLK3 VRK1 PAK5 CDC2/CDK1 PLK2 VRK2 Nek5 PAK6 CDK5 Nek1 CRK7 Nek8 Nek10 MAP2K5 CK1g1 CHED Nek9 CK1d CK1g3 CK1e MEK1/MAP2K1 CK1a CDK9 CK1a2 CCRK MAP2K7 MEK2/MAP2k2 CDK8 MKK3/MAP2K3 CDK11 MKK6/MAP2K6 SEK1/MAP2K4

BARK1/GRK2 CK1 Trb3 SgK495 PASK BARK2/GRK3 Trb1 Lkb1 Trb3 CHK1 SgK494 GRK7 Pim1 RHODK/GRK1 Pim3 Pim2 GRK5 GRK4 PDK1 GRK6

RSKL1 RSKL2

STK33

NIM1 HUNK MSK1 SNRK MSK2

TSSK4

CHK2 PKN3 TTN SSTK PKN2/PRK2PKN1/PRK1 PKG1 SPEG~b TSSK3 p70S6K

PRKY AGC Obscn PKG2 p70S6Kb Obscn~b SPEG MELK PRKX TSSK1 PKD2 PKD1PKD3 PKCe TSSK2 PKCh RSK3 Trio RSK4 RSK1/p90RSK Trad Akt1/PKBg RSK2 CASK smMLCK PKAa AMPKa2 DCAMKL3 PKAb Akt1/PKBa Akt1/PKBb AMPKa1BRSK2 DCAMKL1DCAMKL2 PKCg SGK1 SGK3 BRSK1 NuaK2 SGK2 skMLCK QSK VACAMKL NuaK1 DRAK2 SIK DRAK1 PhKg1 QIK MNK1 CaMK2aCaMK2d PhKg2 PSKH1 PKCa MNK2 PSKH2

SgK085 AurA/Aur2 PKCb CaMK2b caMLCK DAPK1 CaMK2g CaMK4 DAPK2

DAPK3 AurB/Aur1 AurC/Aur3 LATS2LATS1 YANK1 RSK4~b CaMK1b NDR1

AMPK4 YANK2 MARK2 AMPK3 RSK1~b AMPK1 MSK2~b NDR2 RSK3~b YANK3 CAMK RSK2~bMSK1~b CaMK1g MAPKAPK3 MAST3 EphA1 (EPH) MASTL CRIK MAPKAPK2MAPKAPK5 EphA2 (ECK) ROCK1 EphA3 (HEK)

CaMK1d CaMK1a DMPK ROCK2 EphA4 (SEK1) MASR2 EphA5 (EHK1) MAST1 DMPK2 MAST4 EphA6 (EHK2) EphA7 (MDK1) MRCKb EphA8 (EEK) MRCKa EphB1 (ELK) EphB2 (NUK) PDGFRα EphB3 (HEK2) EGFR PDGFRβ HER2 EphB4 (HTK) ROS CSF1R HER3 EphB5 (CEK9) FLT1 EphB6 (MEP) KIT References HER4 ROR1 FLK1 CCK4 INSR TIE FLK2 ROR2 FLT4 IGF1R TEK AXL MCK10 TRKA MET MER FR1 1. S. Shanmugam & K. Gramatikoff, Abgent BioInformatics. TYRO10 RET TRKB RON Musk SKY FR2 TRKC FR3 2. CL. Sawyers, & Dev., 2003; 17: 2998-3010. FGFR4 3. G. Manning, et al., Science 2002; 298: 1912-34. LTK RYK Receptor Tyrosine Kinases ALK LMR1 4. AI. Su, et al., PNAS, 2002; 99; 4465-7. SuRTK106 LMR2 ? C1r-like LMR3 Kinase Ig-like Factor VIII- 5. M. Nakamoto et al., M Res Tech, 2002; 59(1): 58-67. like Glycine- Cysteine EGF-like rich 6. C. Sachsenmaier, Onkologie, 2001; 24(4): 346-55. rich Cadherin Leucine or "YWTD" FNIII- proline-rich Kringle 7. JA. Boutin, Int J Biochem, 1994; 26(10-11): 1203-26. like Acidic