Kinome Array Profiling of Patient-Derived Pancreatic Ductal Adenocarcinoma Identifies Differentially Active Protein Tyrosine Kinases
Abstract
:1. Introduction
2. Results
2.1. PamGene Kinome Activity Profiling Using Protein Tyrosine Kinase PamChip®
2.2. UKA and KRSA Combinatory Analysis
2.3. Expanded PTM-SEA and KEA3 Combinatory Analysis
3. Discussion
3.1. Identification of Lead Candidate Kinases
3.2. Reference Kinases
3.3. Neoteric Kinases
4. Materials and Methods
4.1. Experimental Design
4.2. Cell Lines and Patient-Derived Tissue
4.3. Tyrosine Kinase Array
4.4. Upstream Kinase Identification
4.4.1. Upstream Kinase Analysis (UKA) Pipeline
4.4.2. Post-Translational Modification Signature Enrichment Analysis (PTM-SEA) Pipeline
4.4.3. Kinase Enrichment Analysis Version 3 (KEA3) Pipeline
4.4.4. Kinome Random Sampling Analyzer (KRSA) Pipeline
4.5. Combinatory Analyses
4.6. Peptide Identities, Gene Synonyms, Family Designations, and Other Mapped Data
4.7. Figure Generation
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
PDAC | Pancreatic ductal adenocarcinoma |
KRSA | Kinome Random Sampling Analyzer |
UKA | Upstream Kinase Analysis |
PTM-SEA | Post-Translational Modification Signature Enrichment Analysis |
KEA3 | Kinase Enrichment Analysis Version 3 |
Z | Standard score |
FC | Fold change |
LFC | Log fold change |
R2 | R-squared statistical measure |
HGNC | HUGO Gene Nomenclature Committee |
ssGSEA | Single sample Gene Set Enrichment Analysis |
PDCL5 | Patient-derived pancreatic ductal adenocarcinoma cell line 5 |
PDCL15 | Patient-derived pancreatic ductal adenocarcinoma cell line 15 |
SNP | Single nucleotide polymorphism |
PDX1, IPF1 | Pancreatic and duodenal homeobox 1 transcription factor |
BSA | Bovine serum albumin |
LCK | LCK proto-oncogene, Src family tyrosine kinase |
DDR2 | Discoidin domain receptor tyrosine kinase 2 |
LYN | LYN proto-oncogene, Src family tyrosine kinase |
SRC | SRC proto-oncogene, non-receptor tyrosine kinase |
ABL1 | ABL proto-oncogene 1, non-receptor tyrosine kinase |
TEC | Tec protein tyrosine kinase |
FYN | FYN proto-oncogene, Src family tyrosine kinase |
BLK | BLK proto-oncogene, Src family tyrosine kinase |
TXK | TXK tyrosine kinase |
SRMS | Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites |
PDGFRA | Platelet-derived growth factor receptor alpha |
FRK | Fyn-related Src family tyrosine kinase |
PTK7 | Protein tyrosine kinase 7 (inactive) |
ROS1 | ROS proto-oncogene 1, receptor tyrosine kinase |
TNK2 | Tyrosine kinase non receptor 2 |
ALK | ALK receptor tyrosine kinase |
LTK | Leukocyte receptor tyrosine kinase |
ITK | IL2 inducible T cell kinase |
FLT1 | Fms-related receptor tyrosine kinase 1 |
EPHB1 | EPH receptor B1 |
ABL2 | ABL proto-oncogene 2, non-receptor tyrosine kinase |
HCK | HCK proto-oncogene, Src family tyrosine kinase |
EPHB3 | EPH receptor B3 |
BTK | Bruton tyrosine kinase |
EGFR | Epidermal growth factor receptor |
MST1R | Macrophage stimulating 1 receptor |
INSR | Insulin receptor |
FGR | FGR proto-oncogene, Src family tyrosine kinase |
KIT | KIT proto-oncogene, receptor tyrosine kinase |
FLT4 | Fms-related receptor tyrosine kinase 4 |
FLT3 | Fms-related receptor tyrosine kinase 3 |
RET | Ret proto-oncogene |
EPHA2 | EPH receptor A2 |
PDGFRB | Platelet-derived growth factor receptor beta |
ZAP70 | Zeta chain of T cell receptor-associated protein kinase 70 |
JAK2 | Janus kinase 2 |
KDR | Kinase insert domain receptor |
AXL | AXL receptor tyrosine kinase |
CSK | C-terminal Src kinase |
MET | MET proto-oncogene, receptor tyrosine kinase |
SEV | Sevenless |
SYK | Spleen-associated tyrosine kinase |
VEGFR | Vascular endothelial growth factor receptor |
TYRO3 | TYRO3 protein tyrosine kinase |
EPHB4 | EPH receptor B4 |
PTK6 | Protein tyrosine kinase 6 |
YES1 | YES proto-oncogene 1, Src family tyrosine kinase |
CSF1R | Colony stimulating factor 1 receptor |
FES | FES proto-oncogene, tyrosine kinase |
INSRR | Insulin receptor-related receptor |
FGFR4 | Fibroblast growth factor receptor 4 |
JAK3 | Janus kinase 3 |
MATK | Megakaryocyte-associated tyrosine kinase |
FGFR3 | Fibroblast growth factor receptor 3 |
ERBB3 | Erb-b2 receptor tyrosine kinase 3 |
BMX | BMX nonreceptor tyrosine kinase |
IGF1R | Insulin-like growth factor 1 receptor |
NTRK1 | Neurotrophic receptor tyrosine kinase 1 |
EPHA4 | EPH receptor A4 |
EPHB2 | EPH receptor B2 |
NTRK3 | Neurotrophic receptor tyrosine kinase 3 |
FER | FER tyrosine kinase |
FGFR2 | Fibroblast growth factor receptor 2 |
EPHA1 | EPH receptor A1 |
ERBB4 | Erb-b2 receptor tyrosine kinase 4 |
FGFR1 | Fibroblast growth factor receptor 1 |
DDR1 | Discoidin domain receptor tyrosine kinase 1 |
EPHA5 | EPH receptor A5 |
JAK1 | Janus kinase 1 |
EPHA7 | EPH receptor A7 |
ERBB2 | Erb-b2 receptor tyrosine kinase 2 |
NTRK2 | Neurotrophic receptor tyrosine kinase 2 |
TYK2 | Tyrosine kinase 2 |
PTK2 | Protein tyrosine kinase 2 |
SLTM | SAFB-like transcription modulator |
EPHA8 | EPH receptor A8 |
EPHA3 | EPH receptor A3 |
MERTK | MER proto-oncogene, tyrosine kinase |
RYK | Receptor-like tyrosine kinase |
PTK2B | Protein tyrosine kinase 2 beta |
STYK1 | Serine/threonine/tyrosine kinase 1 |
TEK | TEK receptor tyrosine kinase |
AATK | Apoptosis-associated tyrosine kinase |
MTTP | Microsomal triglyceride transfer protein |
TPM3 | Tropomyosin 3 |
Appendix A
Cell Line | Kinase | Mean Kinase Statistic | Direction |
---|---|---|---|
PDCL15 | BLK | 10.30884201 | Increased |
PANC1 | BLK | 3.809077325 | Increased |
PDCL5 | BLK | 0.963873271 | Increased |
PDCL15 | EGFR | 6.92042103 | Increased |
PANC1 | EGFR | 2.196020549 | Increased |
PDCL5 | EGFR | 0.723998698 | Increased |
PDCL15 | EphA2 | 6.538112723 | Increased |
PANC1 | EphA2 | 2.767994333 | Increased |
PDCL5 | EphA2 | 0.663688934 | Increased |
PDCL15 | FLT4 | 5.969120078 | Increased |
PANC1 | FLT4 | 1.888408842 | Increased |
PDCL5 | FLT4 | 0.754741786 | Increased |
PDCL15 | FRK | 10.54460498 | Increased |
PANC1 | FRK | 3.517514717 | Increased |
PDCL5 | FRK | 0.581814545 | Increased |
PDCL15 | Fyn | 11.52215741 | Increased |
PANC1 | Fyn | 4.046633984 | Increased |
PDCL5 | Fyn | 0.080983021 | Increased |
PDCL15 | InSR | 8.923873567 | Increased |
PANC1 | InSR | 3.024794143 | Increased |
PDCL5 | InSR | 0.508668865 | Increased |
PDCL15 | Lck | 12.35321414 | Increased |
PANC1 | Lck | 4.06073018 | Increased |
PDCL5 | Lck | 0.177602219 | Increased |
PDCL15 | Lyn | 11.88473844 | Increased |
PANC1 | Lyn | 4.172287974 | Increased |
PDCL5 | Lyn | 0.620188468 | Increased |
PDCL15 | PDGFR[alpha] | 14.1657858 | Increased |
PANC1 | PDGFR[alpha] | 4.47805184 | Increased |
PDCL5 | PDGFR[alpha] | −0.21206998 | Decreased |
PDCL15 | Src | 10.51520452 | Increased |
PANC1 | Src | 3.487086518 | Increased |
PDCL5 | Src | 0.34051653 | Increased |
PDCL15 | TEC | 10.09732985 | Increased |
PANC1 | TEC | 3.229557798 | Increased |
PDCL5 | TEC | 0.732187188 | Increased |
PDCL15 | HCK | 10.2005583 | Increased |
PANC1 | HCK | 3.13041308 | Increased |
PDCL5 | HCK | 0.537561913 | Increased |
PDCL15 | Arg | 9.644954083 | Increased |
PANC1 | Arg | 3.436290625 | Increased |
PDCL5 | Arg | 0.713079917 | Increased |
PDCL15 | DDR1 | 7.462484096 | Increased |
PANC1 | DDR1 | 2.528789422 | Increased |
PDCL5 | DDR1 | −0.255600871 | Decreased |
PDCL15 | EphA8 | 9.12751897 | Increased |
PANC1 | EphA8 | 1.855262187 | Increased |
PDCL5 | EphA8 | −0.456838117 | Decreased |
Cell Line | Category | Clinicopathological Data of the Patient of Origin | Standard of Care | Mutational Profile | Ref. |
---|---|---|---|---|---|
PANC1 | Commercial | Age: 56; Gender: Male; Ethnicity: Caucasian; Disease: Epithelioid Carcinoma of Ductal Cell Origin | Surgical resection with or without post-surgical adjuvant therapy | KRAS_G12D; TP53_R273H | [98] |
PDCL15 | Patient Derived | Age: 66; Gender: Male; Ethnicity: Caucasian; Disease: Pancreatic Ductal Adenocarcinoma | Surgical resection with or without post-surgical adjuvant therapy | KRAS_G12D; TP53_WT; | [7,9,11,108] Data Repo |
PDCL5 | Patient Derived | Age: 56; Gender: Male; Ethnicity: Caucasian; Disease: Pancreatic Ductal Adenocarcinoma | Surgical resection with or without post-surgical adjuvant therapy | KRAS_G12V; TP53_G245S | [7,9,11,108] Data Repo |
Appendix B
Cell Line | Kinase | Mean Kinase Statistic | Direction |
---|---|---|---|
AATK | apoptosis associated tyrosine kinase | HGNC:21 | 17q25.3 |
ABL1 | ABL proto-oncogene 1, non-receptor tyrosine kinase | HGNC:76 | 9q34.12 |
ABL2 | ABL proto-oncogene 2, non-receptor tyrosine kinase | HGNC:77 | 1q25.2 |
ALK | ALK receptor tyrosine kinase | HGNC:427 | 2p23.2-p23.1 |
AXL | AXL receptor tyrosine kinase | HGNC:905 | 19q13.2 |
BLK | BLK proto-oncogene, Src family tyrosine kinase | HGNC:1057 | 8p23.1 |
BMX | BMX non-receptor tyrosine kinase | HGNC:1079 | Xp22.2 |
BTK | Bruton tyrosine kinase | HGNC:1133 | Xq22.1 |
CSF1R | colony stimulating factor 1 receptor | HGNC:2433 | 5q32 |
CSK | C-terminal Src kinase | HGNC:2444 | 15q24.1 |
DDR1 | discoidin domain receptor tyrosine kinase 1 | HGNC:2730 | 6p21.33 |
DDR2 | discoidin domain receptor tyrosine kinase 2 | HGNC:2731 | 1q23.3 |
EGFR | epidermal growth factor receptor | HGNC:3236 | 7p11.2 |
EPHA1 | EPH receptor A1 | HGNC:3385 | 7q34-q35 |
EPHA2 | EPH receptor A2 | HGNC:3386 | 1p36.13 |
EPHA3 | EPH receptor A3 | HGNC:3387 | 3p11.1 |
EPHA4 | EPH receptor A4 | HGNC:3388 | 2q36.1 |
EPHA5 | EPH receptor A5 | HGNC:3389 | 4q13.1-q13.2 |
EPHA7 | EPH receptor A7 | HGNC:3390 | 6q16.1 |
EPHA8 | EPH receptor A8 | HGNC:3391 | 1p36.12 |
EPHB1 | EPH receptor B1 | HGNC:3392 | 3q22.2 |
EPHB2 | EPH receptor B2 | HGNC:3393 | 1p36.12 |
EPHB3 | EPH receptor B3 | HGNC:3394 | 3q27.1 |
EPHB4 | EPH receptor B4 | HGNC:3395 | 7q22.1 |
ERBB2 | erb-b2 receptor tyrosine kinase 2 | HGNC:3430 | 17q12 |
ERBB3 | erb-b2 receptor tyrosine kinase 3 | HGNC:3431 | 12q13.2 |
ERBB4 | erb-b2 receptor tyrosine kinase 4 | HGNC:3432 | 2q34 |
FER | FER tyrosine kinase | HGNC:3655 | 5q21.3 |
FES | FES proto-oncogene, tyrosine kinase | HGNC:3657 | 15q26.1 |
FGFR1 | fibroblast growth factor receptor 1 | HGNC:3688 | 8p11.23 |
FGFR2 | fibroblast growth factor receptor 2 | HGNC:3689 | 10q26.13 |
FGFR3 | fibroblast growth factor receptor 3 | HGNC:3690 | 4p16.3 |
FGFR4 | fibroblast growth factor receptor 4 | HGNC:3691 | 5q35.2 |
FGR | FGR proto-oncogene, Src family tyrosine kinase | HGNC:3697 | 1p35.3 |
FLT1 | fms related receptor tyrosine kinase 1 | HGNC:3763 | 13q12.3 |
FLT3 | fms related receptor tyrosine kinase 3 | HGNC:3765 | 13q12.2 |
FLT4 | fms related receptor tyrosine kinase 4 | HGNC:3767 | 5q35.3 |
FRK | fyn related Src family tyrosine kinase | HGNC:3955 | 6q22.1 |
FYN | FYN proto-oncogene, Src family tyrosine kinase | HGNC:4037 | 6q21 |
HCK | HCK proto-oncogene, Src family tyrosine kinase | HGNC:4840 | 20q11.21 |
IGF1R | insulin like growth factor 1 receptor | HGNC:5465 | 15q26.3 |
INSR | insulin receptor | HGNC:6091 | 19p13.2 |
INSRR | insulin receptor related receptor | HGNC:6093 | 1q23.1 |
ITK | IL2 inducible T cell kinase | HGNC:6171 | 5q33.3 |
JAK1 | Janus kinase 1 | HGNC:6190 | 1p31.3 |
JAK2 | Janus kinase 2 | HGNC:6192 | 9p24.1 |
JAK3 | Janus kinase 3 | HGNC:6193 | 19p13.11 |
KDR | kinase insert domain receptor | HGNC:6307 | 4q12 |
KIT | KIT proto-oncogene, receptor tyrosine kinase | HGNC:6342 | 4q12 |
LCK | LCK proto-oncogene, Src family tyrosine kinase | HGNC:6524 | 1p35.2 |
LTK | leukocyte receptor tyrosine kinase | HGNC:6721 | 15q15.1 |
LYN | LYN proto-oncogene, Src family tyrosine kinase | HGNC:6735 | 8q12.1 |
MATK | megakaryocyte-associated tyrosine kinase | HGNC:6906 | 19p13.3 |
MERTK | MER proto-oncogene, tyrosine kinase | HGNC:7027 | 2q13 |
MET | MET proto-oncogene, receptor tyrosine kinase | HGNC:7029 | 7q31 |
MST1R | macrophage stimulating 1 receptor | HGNC:7381 | 3p21.31 |
NTRK1 | neurotrophic receptor tyrosine kinase 1 | HGNC:8031 | 1q23.1 |
NTRK2 | neurotrophic receptor tyrosine kinase 2 | HGNC:8032 | 9q21.33 |
NTRK3 | neurotrophic receptor tyrosine kinase 3 | HGNC:8033 | 15q25.3 |
PDGFRA | platelet derived growth factor receptor alpha | HGNC:8803 | 4q12 |
PDGFRB | platelet derived growth factor receptor beta | HGNC:8804 | 5q32 |
PTK2 | protein tyrosine kinase 2 | HGNC:9611 | 8q24.3 |
PTK2B | protein tyrosine kinase 2 beta | HGNC:9612 | 8p21.2 |
PTK6 | protein tyrosine kinase 6 | HGNC:9617 | 20q13.33 |
PTK7 | protein tyrosine kinase 7 (inactive) | HGNC:9618 | 6p21.1 |
RET | ret proto-oncogene | HGNC:9967 | 10q11.21 |
ROS1 | ROS proto-oncogene 1, receptor tyrosine kinase | HGNC:10261 | 6q22.1 |
RYK | receptor like tyrosine kinase | HGNC:10481 | 3q22.2 |
SLTM | SAFB like transcription modulator | HGNC:20709 | 15q22.1 |
SRC | SRC proto-oncogene, non-receptor tyrosine kinase | HGNC:11283 | 20q11.23 |
SRMS | src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites | HGNC:11298 | 20q13.33 |
STYK1 | serine/threonine/tyrosine kinase 1 | HGNC:18889 | 12p13.2 |
SYK | spleen associated tyrosine kinase | HGNC:11491 | 9q22.2 |
TEC | tec protein tyrosine kinase | HGNC:11719 | 4p12-p11 |
TEK | TEK receptor tyrosine kinase | HGNC:11724 | 9p21.2 |
TNK2 | tyrosine kinase non receptor 2 | HGNC:19297 | 3q29 |
TXK | TXK tyrosine kinase | HGNC:12434 | 4p12 |
TYK2 | tyrosine kinase 2 | HGNC:12440 | 19p13.2 |
TYRO3 | TYRO3 protein tyrosine kinase | HGNC:12446 | 15q15.1 |
YES1 | YES proto-oncogene 1, Src family tyrosine kinase | HGNC:12841 | 18p11.32 |
ZAP70 | zeta chain of T cell receptor associated protein kinase 70 | HGNC:12858 | 2q11.2 |
Pipeline | Default | Standardized |
---|---|---|
KRSA | TEC | TEC |
KRSA | DDR | DDR |
KRSA | SRC | SRC |
KRSA | ABL | ABL |
KRSA | PDGFR | PDGFR |
KRSA | FRK | FRK |
KRSA | JAK | JAK |
KRSA | INSR | INSR |
KRSA | FGFR | FGFR |
KRSA | TRK | TRK |
KRSA | ACK | ACK |
KRSA | SEV | SEV |
KRSA | VEGFR | VEGFR |
KRSA | AXL | AXL |
KRSA | FAK | FAK |
KRSA | MET | MET |
KRSA | EPH | EPH |
KRSA | RET | RET |
KRSA | SYK | SYK |
KRSA | RYK | RYK |
KRSA | FER | FER |
KRSA | ALK | ALK |
KRSA | EGFR | EGFR |
KRSA | CSK | CSK |
UKA | Lck | Lck |
UKA | Lyn | Lyn |
UKA | TEC | TEC |
UKA | FRK | FRK |
UKA | Tyro3/Sky | TYRO3 |
UKA | PDGFR[alpha] | PDGFRa |
UKA | Src | Src |
UKA | Fyn | Fyn |
UKA | Abl | ABL1 |
UKA | CCK4/PTK7 | PTK7 |
UKA | Ron | MST1R |
UKA | CTK | MATK |
UKA | Axl | Axl |
UKA | Fes | Fes |
UKA | BLK | BLK |
UKA | TXK | TXK |
UKA | Arg | ABL2 |
UKA | HCK | HCK |
UKA | HER3 | ERBB3 |
UKA | Syk | Syk |
UKA | Srm | SRMS |
UKA | EphA8 | EphA8 |
UKA | ZAP70 | ZAP70 |
UKA | CSK | CSK |
UKA | EphB4 | EphB4 |
UKA | Mer | MERTK |
UKA | PDGFR[beta] | PDGFRb |
UKA | Met | Met |
UKA | FAK1 | PTK2 |
UKA | RYK | RYK |
UKA | Fgr | Fgr |
UKA | Yes | YES1 |
UKA | InSR | InSR |
UKA | Ret | Ret |
UKA | DDR1 | DDR1 |
UKA | LTK | LTK |
UKA | FGFR2 | FGFR2 |
UKA | Fer | Fer |
UKA | Kit | Kit |
UKA | EphA5 | EphA5 |
UKA | EphB1 | EphB1 |
UKA | IGF1R | IGF1R |
UKA | Ros | ROS1 |
UKA | FmS/CSFR | CSF1R |
UKA | TRKB | NTRK2 |
UKA | EphA4 | EphA4 |
UKA | JAK2 | JAK2 |
UKA | ALK | ALK |
UKA | FGFR3 | FGFR3 |
UKA | Etk/BMX | BMX |
UKA | BTK | BTK |
UKA | FGFR1 | FGFR1 |
UKA | TRKC | NTRK3 |
UKA | EphB3 | EphB3 |
UKA | EphA2 | EphA2 |
UKA | ITK | ITK |
UKA | Lmr1 | AATK |
UKA | EphA1 | EphA1 |
UKA | KDR | KDR |
UKA | FGFR4 | FGFR4 |
UKA | FLT3 | FLT3 |
UKA | FAK2 | PTK2B |
UKA | JAK3 | JAK3 |
UKA | HER2 | ERBB2 |
UKA | IRR | INSRR |
UKA | TRKA | NTRK1 |
UKA | JAK1~b | JAK1 |
UKA | HER4 | ERBB4 |
UKA | Tyk2 | Tyk2 |
UKA | EphA3 | EphA3 |
UKA | FLT4 | FLT4 |
UKA | Brk | PTK6 |
UKA | EphA7 | EphA7 |
UKA | EphB2 | EphB2 |
UKA | EGFR | EGFR |
UKA | FLT1 | FLT1 |
PTM-SEA | ZAP70 | ZAP70 |
PTM-SEA | VEGFR2/KDR | KDR |
PTM-SEA | TrkA/NTRK1 | NTRK1 |
PTM-SEA | Syk/SYK | SYK |
PTM-SEA | Src/SRC | SRC |
PTM-SEA | Ret/RET | RET |
PTM-SEA | PDGFRB | PDGFRB |
PTM-SEA | PDGFRA | PDGFRA |
PTM-SEA | MKK4/MAP2K4 | MAP2K4 |
PTM-SEA | Met/MET | MET |
PTM-SEA | Mer/MERTK | MERTK |
PTM-SEA | MEK1/MAP2K1 | MAP2K1 |
PTM-SEA | LYN | LYN |
PTM-SEA | Lck/LCK | LCK |
PTM-SEA | JAK3 | JAK3 |
PTM-SEA | JAK2 | JAK2 |
PTM-SEA | INSR | INSR |
PTM-SEA | IGF1R | IGF1R |
PTM-SEA | HER2/ERBB2 | ERBB2 |
PTM-SEA | Fyn/FYN | FYN |
PTM-SEA | Fer/FER | FER |
PTM-SEA | Etk/BMX | BMX |
PTM-SEA | EphA2/EPHA2 | EPHA2 |
PTM-SEA | EGFR | EGFR |
PTM-SEA | CSK | CSK |
PTM-SEA | Chk1/CHEK1 | CHEK1 |
PTM-SEA | AXL | AXL |
PTM-SEA | ALK | ALK |
PTM-SEA | Abl/ABL1 | ABL1 |
KEA3 | NTRK1 | NTRK1 |
KEA3 | FLT3 | FLT3 |
KEA3 | DDR2 | DDR2 |
KEA3 | KIT | KIT |
KEA3 | PDGFRA | PDGFRA |
KEA3 | MATK | MATK |
KEA3 | EPHB3 | EPHB3 |
KEA3 | MST1R | MST1R |
KEA3 | FES | FES |
KEA3 | FLT4 | FLT4 |
KEA3 | SRC | SRC |
KEA3 | TXK | TXK |
KEA3 | NTRK3 | NTRK3 |
KEA3 | KDR | KDR |
KEA3 | RET | RET |
KEA3 | LCK | LCK |
KEA3 | ABL1 | ABL1 |
KEA3 | EPHA2 | EPHA2 |
KEA3 | SRMS | SRMS |
KEA3 | EPHB2 | EPHB2 |
KEA3 | FYN | FYN |
KEA3 | EGFR | EGFR |
KEA3 | FLT1 | FLT1 |
KEA3 | FER | FER |
KEA3 | INSR | INSR |
KEA3 | FGFR4 | FGFR4 |
KEA3 | ITK | ITK |
KEA3 | EPHB1 | EPHB1 |
KEA3 | CSF1R | CSF1R |
KEA3 | PTK6 | PTK6 |
KEA3 | CSK | CSK |
KEA3 | ERBB2 | ERBB2 |
KEA3 | NTRK2 | NTRK2 |
KEA3 | TYRO3 | TYRO3 |
KEA3 | BTK | BTK |
KEA3 | JAK2 | JAK2 |
KEA3 | SYK | SYK |
KEA3 | LYN | LYN |
KEA3 | FGFR3 | FGFR3 |
KEA3 | PTK2 | PTK2 |
KEA3 | FGR | FGR |
KEA3 | ERBB4 | ERBB4 |
KEA3 | YES1 | YES1 |
KEA3 | ZAP70 | ZAP70 |
KEA3 | JAK3 | JAK3 |
KEA3 | MET | MET |
KEA3 | IGF1R | IGF1R |
KEA3 | TEC | TEC |
KEA3 | AXL | AXL |
KEA3 | ALK | ALK |
KEA3 | PTK2B | PTK2B |
KEA3 | PDGFRB | PDGFRB |
KEA3 | STYK1 | STYK1 |
KEA3 | MERTK | MERTK |
KEA3 | BMX | BMX |
KEA3 | EPHA3 | EPHA3 |
KEA3 | ABL2 | ABL2 |
KEA3 | FGFR1 | FGFR1 |
KEA3 | EPHA4 | EPHA4 |
KEA3 | TYK2 | TYK2 |
KEA3 | FRK | FRK |
KEA3 | FGFR2 | FGFR2 |
KEA3 | TNK2 | TNK2 |
KEA3 | JAK1 | JAK1 |
KEA3 | DDR1 | DDR1 |
KEA3 | BLK | BLK |
KEA3 | HCK | HCK |
KEA3 | EPHA8 | EPHA8 |
KEA3 | TEK | TEK |
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Cell Line | Rank | Kinase | Family | Average | KRSA | UKA |
---|---|---|---|---|---|---|
PANC1 | #1 | LCK | SRC | 96% | 91% | 100% |
PANC1 | #2 | DDR2 | DDR | 96% | 96% | |
PANC1 | #3 | LYN | SRC | 95% | 91% | 99% |
PANC1 | #4 | SRC | SRC | 92% | 91% | 92% |
PANC1 | #5 | ABL1 | ABL | 91% | 87% | 95% |
PANC1 | #6 | TEC | TEC | 90% | 100% | 80% |
PANC1 | #7 | FYN | SRC | 90% | 91% | 88% |
PANC1 | #8 | BLK | SRC | 89% | 91% | 87% |
PANC1 | #9 | TXK | TEC | 89% | 100% | 77% |
PANC1 | #10 | SRMS | SRC | 88% | 91% | 85% |
PDCL15 | #1 | DDR2 | DDR | 100% | 100% | - |
PDCL15 | #2 | LCK | SRC | 98% | 96% | 100% |
PDCL15 | #3 | LYN | SRC | 97% | 96% | 99% |
PDCL15 | #4 | TEC | TEC | 94% | 91% | 97% |
PDCL15 | #5 | SRC | SRC | 94% | 96% | 92% |
PDCL15 | #6 | FYN | SRC | 93% | 96% | 91% |
PDCL15 | #7 | PDGFRA | PDGFR | 90% | 87% | 93% |
PDCL15 | #8 | FRK | FRK | 89% | 83% | 96% |
PDCL15 | #9 | BLK | SRC | 88% | 96% | 81% |
PDCL15 | #10 | PTK7 | PTK7 | 88% | - | 88% |
PDCL5 | #1 | PTK7 | PTK7 | 99% | - | 99% |
PDCL5 | #2 | ROS1 | SEV | 97% | 100% | 95% |
PDCL5 | #3 | TNK2 | ACK | 96% | 96% | - |
PDCL5 | #4 | DDR2 | DDR | 87% | 87% | - |
PDCL5 | #5 | ALK | ALK | 86% | 74% | 97% |
PDCL5 | #6 | TXK | TEC | 83% | 65% | 100% |
PDCL5 | #7 | LTK | ALK | 80% | 74% | 86% |
PDCL5 | #8 | ITK | TEC | 79% | 65% | 93% |
PDCL5 | #9 | FLT1 | VEGFR | 78% | 91% | 65% |
PDCL5 | #10 | EPHB1 | EPH | 76% | 61% | 92% |
Patient-Derived | #1 | PTK7 | PTK7 | 100% | - | 100% |
Patient-Derived | #2 | DDR2 | DDR | 100% | 100% | - |
Patient-Derived | #3 | LYN | SRC | 96% | 96% | 96% |
Patient-Derived | #4 | TXK | TEC | 95% | 91% | 99% |
Patient-Derived | #5 | TEC | TEC | 94% | 91% | 97% |
Patient-Derived | #6 | LCK | SRC | 92% | 96% | 88% |
Patient-Derived | #7 | BLK | SRC | 91% | 96% | 87% |
Patient-Derived | #8 | SRMS | SRC | 87% | 96% | 79% |
Patient-Derived | #9 | ITK | TEC | 86% | 91% | 80% |
Patient-Derived | #10 | FRK | FRK | 84% | 78% | 91% |
All | #1 | DDR2 | DDR | 100% | 100% | - |
All | #2 | TXK | TEC | 96% | 96% | 97% |
All | #3 | PTK7 | PTK7 | 96% | - | 96% |
All | #4 | LYN | SRC | 96% | 91% | 100% |
All | #5 | LCK | SRC | 95% | 91% | 99% |
All | #6 | TEC | TEC | 93% | 96% | 91% |
All | #7 | BLK | SRC | 90% | 91% | 88% |
All | #8 | SRMS | SRC | 88% | 91% | 84% |
All | #9 | FRK | FRK | 87% | 83% | 92% |
All | #10 | PDGFRA | PDGFR | 84% | 87% | 81% |
Cell Line | Rank | Kinase | Family | Weighted Average | KRSA | UKA |
---|---|---|---|---|---|---|
PANC1 | #1 | LCK | SRC | 96% | 91% | 100% |
PANC1 | #2 | LYN | SRC | 95% | 91% | 99% |
PANC1 | #3 | SRC | SRC | 92% | 91% | 92% |
PANC1 | #4 | ABL1 | ABL | 91% | 87% | 95% |
PANC1 | #5 | TEC | TEC | 90% | 100% | 80% |
PANC1 | #6 | FYN | SRC | 90% | 91% | 88% |
PANC1 | #7 | BLK | SRC | 89% | 91% | 87% |
PANC1 | #8 | TXK | TEC | 89% | 100% | 77% |
PANC1 | #9 | SRMS | SRC | 88% | 91% | 85% |
PANC1 | #10 | ABL2 | ABL | 88% | 87% | 89% |
PDCL15 | #1 | LCK | SRC | 98% | 96% | 100% |
PDCL15 | #2 | LYN | SRC | 97% | 96% | 99% |
PDCL15 | #3 | TEC | TEC | 94% | 91% | 97% |
PDCL15 | #4 | SRC | SRC | 94% | 96% | 92% |
PDCL15 | #5 | FYN | SRC | 93% | 96% | 91% |
PDCL15 | #6 | PDGFRA | PDGFR | 90% | 87% | 93% |
PDCL15 | #7 | FRK | FRK | 89% | 83% | 96% |
PDCL15 | #8 | BLK | SRC | 88% | 96% | 81% |
PDCL15 | #9 | HCK | SRC | 86% | 96% | 77% |
PDCL15 | #10 | TXK | TEC | 86% | 91% | 80% |
PDCL5 | #1 | ROS1 | SEV | 97% | 100% | 95% |
PDCL5 | #2 | ALK | ALK | 86% | 74% | 97% |
PDCL5 | #3 | TXK | TEC | 83% | 65% | 100% |
PDCL5 | #4 | LTK | ALK | 80% | 74% | 86% |
PDCL5 | #5 | ITK | TEC | 79% | 65% | 93% |
PDCL5 | #6 | FLT1 | VEGFR | 78% | 91% | 65% |
PDCL5 | #7 | EPHB1 | EPH | 76% | 61% | 92% |
PDCL5 | #8 | EPHB3 | EPH | 74% | 61% | 88% |
PDCL5 | #9 | BTK | TEC | 72% | 65% | 78% |
PDCL5 | #10 | EGFR | EGFR | 70% | 83% | 58% |
Patient-Derived | #1 | LYN | SRC | 96% | 96% | 96% |
Patient-Derived | #2 | TXK | TEC | 95% | 91% | 99% |
Patient-Derived | #3 | TEC | TEC | 94% | 91% | 97% |
Patient-Derived | #4 | LCK | SRC | 92% | 96% | 88% |
Patient-Derived | #5 | BLK | SRC | 91% | 96% | 87% |
Patient-Derived | #6 | SRMS | SRC | 87% | 96% | 79% |
Patient-Derived | #7 | ITK | TEC | 86% | 91% | 80% |
Patient-Derived | #8 | FRK | FRK | 84% | 78% | 91% |
Patient-Derived | #9 | ROS1 | SEV | 80% | 74% | 85% |
Patient-Derived | #10 | HCK | SRC | 78% | 96% | 60% |
All | #1 | TXK | TEC | 96% | 96% | 97% |
All | #2 | LYN | SRC | 96% | 91% | 100% |
All | #3 | LCK | SRC | 95% | 91% | 99% |
All | #4 | TEC | TEC | 93% | 96% | 91% |
All | #5 | BLK | SRC | 90% | 91% | 88% |
All | #6 | SRMS | SRC | 88% | 91% | 84% |
All | #7 | FRK | FRK | 87% | 83% | 92% |
All | #8 | PDGFRA | PDGFR | 84% | 87% | 81% |
All | #9 | SRC | SRC | 84% | 91% | 76% |
All | #10 | ABL1 | ABL | 84% | 74% | 93% |
Cell Line | Rank | Kinase | Family | Average | KRSA | UKA | PTM-SEA | KEA3 |
---|---|---|---|---|---|---|---|---|
PANC1 | #1 | DDR2 | DDR | 97% | 96% | - | - | 98% |
PANC1 | #2 | TXK | TEC | 89% | 100% | 77% | - | 90% |
PANC1 | #3 | SRMS | SRC | 86% | 91% | 85% | - | 81% |
PANC1 | #4 | SRC | SRC | 82% | 91% | 92% | 55% | 91% |
PANC1 | #5 | FYN | SRC | 81% | 91% | 88% | 68% | 78% |
PANC1 | #6 | MST1R | MET | 76% | 35% | 97% | - | 95% |
PANC1 | #7 | INSR | INSR | 75% | 70% | 64% | 95% | 72% |
PANC1 | #8 | ABL1 | ABL | 75% | 87% | 95% | 36% | 82% |
PANC1 | #9 | FGR | SRC | 73% | 91% | 83% | - | 45% |
PANC1 | #10 | KIT | PDGFR | 72% | 83% | 35% | - | 97% |
PDCL15 | #1 | DDR2 | DDR | 99% | 100% | - | 98% | |
PDCL15 | #2 | SRC | SRC | 90% | 96% | 92% | 82% | 90% |
PDCL15 | #3 | PTK7 | PTK7 | 88% | - | 88% | - | |
PDCL15 | #4 | TXK | TEC | 88% | 91% | 80% | - | 92% |
PDCL15 | #5 | PDGFRA | PDGFR | 86% | 87% | 93% | 68% | 97% |
PDCL15 | #6 | MST1R | MET | 86% | 78% | 87% | - | 93% |
PDCL15 | #7 | SRMS | SRC | 84% | 96% | 73% | - | 82% |
PDCL15 | #8 | KIT | PDGFR | 78% | 87% | 49% | - | 97% |
PDCL15 | #9 | INSR | INSR | 73% | 70% | 57% | 100% | 65% |
PDCL15 | #10 | TEC | TEC | 72% | 91% | 97% | - | 28% |
PDCL5 | #1 | PTK7 | PTK7 | 99% | - | 99% | - | - |
PDCL5 | #2 | ROS1 | SEV | 97% | 100% | 95% | - | - |
PDCL5 | #3 | DDR2 | DDR | 92% | 87% | - | - | 97% |
PDCL5 | #4 | TXK | TEC | 87% | 65% | 100% | - | 95% |
PDCL5 | #5 | EPHB3 | EPH | 82% | 61% | 88% | - | 98% |
PDCL5 | #6 | LTK | ALK | 80% | 74% | 86% | - | - |
PDCL5 | #7 | EPHB1 | EPH | 76% | 61% | 92% | - | 76% |
PDCL5 | #8 | FLT4 | VEGFR | 76% | 91% | 43% | - | 93% |
PDCL5 | #9 | ITK | TEC | 72% | 65% | 93% | - | 57% |
PDCL5 | #10 | FLT1 | VEGFR | 72% | 91% | 65% | - | 59% |
Patient-Derived | #1 | PTK7 | PTK7 | 100% | - | 100% | - | - |
Patient-Derived | #2 | DDR2 | DDR | 99% | 100% | - | - | 97% |
Patient-Derived | #3 | TXK | TEC | 92% | 91% | 99% | - | 85% |
Patient-Derived | #4 | SRMS | SRC | 84% | 96% | 79% | - | 76% |
Patient-Derived | #5 | LCK | SRC | 80% | 96% | 88% | 60% | 78% |
Patient-Derived | #6 | ROS1 | SEV | 80% | 74% | 85% | - | - |
Patient-Derived | #7 | SRC | SRC | 79% | 96% | 45% | 96% | 81% |
Patient-Derived | #8 | EPHB3 | EPH | 77% | 65% | 75% | - | 93% |
Patient-Derived | #9 | FLT3 | PDGFR | 74% | 87% | 36% | - | 99% |
Patient-Derived | #10 | ITK | TEC | 74% | 91% | 80% | - | 50% |
All | #1 | DDR2 | DDR | 99% | 100% | - | - | 97% |
All | #2 | PTK7 | PTK7 | 96% | - | 96% | - | - |
All | #3 | TXK | TEC | 93% | 96% | 97% | - | 85% |
All | #4 | SRC | SRC | 85% | 91% | 76% | 91% | 82% |
All | #5 | SRMS | SRC | 84% | 91% | 84% | - | 76% |
All | #6 | LCK | SRC | 81% | 91% | 99% | 55% | 78% |
All | #7 | PDGFRA | PDGFR | 75% | 87% | 81% | 36% | 96% |
All | #8 | ROS1 | SEV | 74% | 70% | 79% | - | - |
All | #9 | FLT3 | PDGFR | 73% | 87% | 33% | - | 99% |
All | #10 | ITK | TEC | 72% | 96% | 65% | - | 56% |
Cell Line | Rank | Kinase | Family | Weighted Average | KRSA | UKA | PTM-SEA | KEA3 |
---|---|---|---|---|---|---|---|---|
PANC1 | #1 | SRC | SRC | 82% | 91% | 92% | 55% | 91% |
PANC1 | #2 | FYN | SRC | 81% | 91% | 88% | 68% | 78% |
PANC1 | #3 | INSR | INSR | 75% | 70% | 64% | 95% | 72% |
PANC1 | #4 | ABL1 | ABL | 75% | 87% | 95% | 36% | 82% |
PANC1 | #5 | LCK | SRC | 71% | 91% | 100% | 9% | 85% |
PANC1 | #6 | PDGFRA | PDGFR | 70% | 83% | 91% | 9% | 97% |
PANC1 | #7 | TXK | TEC | 67% | 100% | 77% | - | 90% |
PANC1 | #8 | RET | RET | 67% | 26% | 77% | 77% | 87% |
PANC1 | #9 | EPHA2 | EPH | 65% | 30% | 59% | 91% | 81% |
PANC1 | #10 | SRMS | SRC | 64% | 91% | 85% | - | 81% |
PDCL15 | #1 | SRC | SRC | 90% | 96% | 92% | 82% | 90% |
PDCL15 | #2 | PDGFRA | PDGFR | 86% | 87% | 93% | 68% | 97% |
PDCL15 | #3 | INSR | INSR | 73% | 70% | 57% | 100% | 65% |
PDCL15 | #4 | LYN | SRC | 72% | 96% | 99% | 59% | 34% |
PDCL15 | #5 | PDGFRB | PDGFR | 71% | 87% | 65% | 91% | 41% |
PDCL15 | #6 | LCK | SRC | 70% | 96% | 100% | 0% | 85% |
PDCL15 | #7 | EPHA2 | EPH | 69% | 74% | 28% | 91% | 82% |
PDCL15 | #8 | TXK | TEC | 66% | 91% | 80% | - | 92% |
PDCL15 | #9 | FYN | SRC | 66% | 96% | 91% | 0% | 76% |
PDCL15 | #10 | MST1R | MET | 64% | 78% | 87% | - | 93% |
PDCL5 | #1 | ALK | ALK | 70% | 74% | 97% | 63% | 45% |
PDCL5 | #2 | ZAP70 | SYK | 65% | 52% | 69% | 70% | 70% |
PDCL5 | #3 | TXK | TEC | 65% | 65% | 100% | - | 95% |
PDCL5 | #4 | JAK2 | JAK | 65% | 43% | 91% | 53% | 73% |
PDCL5 | #5 | EGFR | EGFR | 62% | 83% | 58% | 67% | 42% |
PDCL5 | #6 | KDR | VEGFR | 62% | 91% | 39% | 30% | 89% |
PDCL5 | #7 | EPHB3 | EPH | 62% | 61% | 88% | - | 98% |
PDCL5 | #8 | AXL | AXL | 59% | 57% | 28% | 97% | 54% |
PDCL5 | #9 | CSK | CSK | 59% | 13% | 72% | 87% | 63% |
PDCL5 | #10 | INSR | INSR | 58% | 78% | 23% | 70% | 61% |
Patient-Derived | #1 | LCK | SRC | 80% | 96% | 88% | 60% | 78% |
Patient-Derived | #2 | SRC | SRC | 79% | 96% | 45% | 96% | 81% |
Patient-Derived | #3 | LYN | SRC | 72% | 96% | 96% | 64% | 32% |
Patient-Derived | #4 | PDGFRA | PDGFR | 72% | 87% | 53% | 52% | 96% |
Patient-Derived | #5 | TXK | TEC | 69% | 91% | 99% | - | 85% |
Patient-Derived | #6 | INSR | INSR | 66% | 83% | 21% | 100% | 60% |
Patient-Derived | #7 | EGFR | EGFR | 64% | 61% | 41% | 92% | 63% |
Patient-Derived | #8 | EPHA2 | EPH | 64% | 65% | 39% | 80% | 72% |
Patient-Derived | #9 | SRMS | SRC | 63% | 96% | 79% | - | 76% |
Patient-Derived | #10 | EPHB3 | EPH | 58% | 65% | 75% | - | 93% |
All | #1 | SRC | SRC | 85% | 91% | 76% | 91% | 82% |
All | #2 | LCK | SRC | 81% | 91% | 99% | 55% | 78% |
All | #3 | PDGFRA | PDGFR | 75% | 87% | 81% | 36% | 96% |
All | #4 | LYN | SRC | 72% | 91% | 100% | 59% | 38% |
All | #5 | TXK | TEC | 70% | 96% | 97% | - | 85% |
All | #6 | INSR | INSR | 68% | 78% | 32% | 100% | 62% |
All | #7 | EPHA2 | EPH | 64% | 57% | 43% | 86% | 72% |
All | #8 | JAK2 | JAK | 64% | 61% | 68% | 64% | 63% |
All | #9 | SRMS | SRC | 63% | 91% | 84% | - | 76% |
All | #10 | FYN | SRC | 62% | 91% | 59% | 23% | 74% |
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Creeden, J.F.; Alganem, K.; Imami, A.S.; Brunicardi, F.C.; Liu, S.-H.; Shukla, R.; Tomar, T.; Naji, F.; McCullumsmith, R.E. Kinome Array Profiling of Patient-Derived Pancreatic Ductal Adenocarcinoma Identifies Differentially Active Protein Tyrosine Kinases. Int. J. Mol. Sci. 2020, 21, 8679. https://doi.org/10.3390/ijms21228679
Creeden JF, Alganem K, Imami AS, Brunicardi FC, Liu S-H, Shukla R, Tomar T, Naji F, McCullumsmith RE. Kinome Array Profiling of Patient-Derived Pancreatic Ductal Adenocarcinoma Identifies Differentially Active Protein Tyrosine Kinases. International Journal of Molecular Sciences. 2020; 21(22):8679. https://doi.org/10.3390/ijms21228679
Chicago/Turabian StyleCreeden, Justin F., Khaled Alganem, Ali S. Imami, F. Charles Brunicardi, Shi-He Liu, Rammohan Shukla, Tushar Tomar, Faris Naji, and Robert E. McCullumsmith. 2020. "Kinome Array Profiling of Patient-Derived Pancreatic Ductal Adenocarcinoma Identifies Differentially Active Protein Tyrosine Kinases" International Journal of Molecular Sciences 21, no. 22: 8679. https://doi.org/10.3390/ijms21228679