REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
p-CREB/ATF1 (Ser133 of CREB/Ser63 of ATF1), Clone J151-21	BD Biosciences	Cat# 558436; RRID: AB_647204
p-STAT5 (Tyr694), Clone 47/Stat5	BD Biosciences	Cat# 612567; RRID: AB_399858
p-SRC (Tyr418), Clone SC1T2M3	eBioscience	Cat# 14-9034-82; RRID: AB_2572916
p-FAK (Tyr397), Polyclonal	Cell Signaling Technology	Cat# 3283; RRID: AB_2173659
p-MEK1/2 (Ser221), Clone 166F8	Cell Signaling Technology	Cat# 2338; RRID: AB_490903
p-MAPKAPK2 (Thr334), Clone 27B7	Cell Signaling Technology	Cat# 3007; RRID: AB_490936
p-p70S6K (Thr389), Clone 1A5	Cell Signaling Technology	Cat# 9206; RRID: AB_2285392
p-MKK4 (Ser257/Thr261), Clone C36C11	Cell Signaling Technology	Cat# 4514; RRID: AB_2140946
p-STAT1 (Ser727), Polyclonal	Cell Signaling Technology	Cat# 9177; RRID: AB_2197983
p-p53 (Ser15), Clone 16G8	Cell Signaling Technology	Cat# 4030; RRID: AB_10694347
p-NFκB (Ser529), Clone K10-895.12.50	BD Biosciences	Cat# 558393; RRID: AB_647284
p-p38 (Thr180/Tyr182), Clone 36/p38	BD Biosciences	Cat# 612289; RRID: AB_399606
p-AMPKα (Thr172), Clone 40H9	Cell Signaling Technology	Cat# 5256; RRID: AB_10705605
p-AKT (Ser473), Clone D9E	Cell Signaling Technology	Cat# 5012; RRID: AB_2224726
p-ERK1/2 (Thr202/Tyr204), Clone 20A	BD Biosciences	Cat# 612359; RRID: AB_399648
p-MARCKS (Ser167/170), Clone D13E4	Cell Signaling Technology	Cat# 8722; RRID: AB_10999091
cyclin B1, Clone GNS-11	BD Biosciences	Cat# 554178; RRID: AB_395289
p-GSK3β (Ser9), Clone D85E12	Cell Signaling Technology	Cat# 5558; RRID: AB_10013750
GAPDH, Clone 6C5	Thermo Fisher Scientific	Cat# AM4300; RRID: AB_2536381
p-MKK3/6 (Ser189 of MKK3/Ser207 of MKK6), Clone D8E9	Cell Signaling Technology	Cat# 12280
p-PDK1 (Ser241), Clone J66-653.44.22	BD Biosciences	Cat# 558395; RRID: AB_647291
p-BTK/ITK (Tyr551 of BTK/Tyr551 of ITK), Clone 24a/BTK	BD Biosciences	Cat# 558034; RRID: AB_2067823
p-p90RSK (Ser380), Clone D5D8	Cell Signaling Technology	Cat# 12032
p-SMAD2/3 (Ser465/467 of SMAD2/Ser423/425 of SMAD3), Clone D27F4	Cell Signaling Technology	Cat# 8828; RRID: AB_2631089
β-catenin (Non-phospho Ser33/37/Thr41), Clone D13A1	Cell Signaling Technology	Cat# 8814; RRID: AB_11127203
p-STAT3 (Tyr705), Clone 4/P-STAT3	BD Biosciences	Cat# 612356; RRID: AB_399645
p-JNK (Thr183/Tyr185), Clone G9	Cell Signaling Technology	Cat# 9255; RRID: AB_2307321
p-PLCγ2 (Tyr759), Clone K86-689.37	BD Biosciences	Cat# 558490; RRID: AB_647226
GFP, Clone FM264G	BioLegend	Cat# 338002; RRID: AB_1279414
p-HH3 (Ser28), Clone HTA28	BioLegend	Cat# 641002; RRID: AB_1227659
p-S6 (Ser235/Ser236), Clone N7-548	BD Biosciences	Custom made
cleaved PARP, Clone F21-852	BD Biosciences	Cat# 552596; RRID: AB_394437
p-mTOR (Ser2448), Clone D9C2	Cell Signaling Technology	Cat# 5536; RRID: AB_10691552
p-c-RAF (Ser259), Clone Polyclonal	Thermo Fisher Scientific	Cat# 44-502; RRID: AB_2533669
p-RB (Ser807/811), Clone D20B12	Cell Signaling Technology	Cat# 8516; RRID: AB_11178658
p-4EBP1 (Thr37/46), Clone 236B4	Cell Signaling Technology	Cat# 2855; RRID: AB_560835
Chemicals, Peptides, and Recombinant Proteins
Paraformaldehyde	Electron Microscopy Sciences	Cat# 15710
Maleimido mono amide DOTA (mDOTA)	Macrocyclics	Cat# B-272
Iridium	Fluidigm	Cat# 201192A
Maxpar X8 Multimetal labeling kit	Fluidigm	Cat# 201300
Lanthanide (III) metal isotopes as chloride salts	Fluidigm	N/A
jetPRIME	PolyPlus	Cat# 114-15
X-treme GENE HP	Roche	Cat# 6366236001
Recombinant Murine EGF	Peprotech	Cat# 315-09
vemurafenib	Selleckchem	Cat# S1267
CI1040	Selleckchem	Cat# S1020
Deposited Data
Integrated raw data and preprocessed data	This paper	https://doi.org/10.17632/3kh7ypz232.1
Experimental Models: Cell Lines
HEK293T	ATCC	Cat# CRL-3216, RRID:CVCL_0063
A375	A gift from Dr. Lukas Sommer	N/A
Recombinant DNA
The human kinase library plasmid kit	Addgene	Kit# 1000000014
ORFeome Human Entry Collection Phosphatase	Dharmacon	Cat# OHS4941
pDEST pcDNA5 FRT TO-eGFP	A gift from Dr. Anne-Claude Gingras	N/A
pDEST 3′ Triple Flag pcDNA5 FRT TO	A gift from Dr. Anne-Claude Gingras	N/A
pFLAG-CMV-hErk1 (K71R)	Addgene	Plasmid # 49329
pCIG AKT3 (K177M)	Addgene	Plasmid # 73051
pMCL-HA-MAPKK1-8E (K97M)	Addgene	Plasmid # 40811
IRES-GFP-AXL-KD (K567R)	Addgene	Plasmid # 65498
FLAG.PKCepsilon.K/W (K437W)	Addgene	Plasmid # 10796
Software and Algorithms
Cytobank	Cytobank	https://www.cytobank.org/
Concatenation tool	Cytobank	https://support.cytobank.org/hc/en-us/articles/206336147-FCS-file-concatenation-tool
Normalizer	Finck et al., 2013	https://github.com/nolanlab/bead-normalization/releases
Single cell debarcoder	Zunder et al., 2015	https://github.com/nolanlab/single-cell-debarcoder
BP-R2 analysis	Lun et al., 2017	https://github.com/BodenmillerGroup/Adnet
t-SNE	van der Maaten and Hinton, 2008	https://github.com/jkrijthe/Rtsne
STRING	Szklarczyk et al., 2017	https://string-db.org/
OmniPath	Türei et al., 2016	http://omnipathdb.org/
Shape-based clustering	Genolini et al., 2015	R package ‘kml’