REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Rabbit anti-MYC	Cell Signaling Tech.	Cat# 5605
Mouse anti-MYC	Invitrogen	Cat# MA1–980
Mouse anti-β-actin	Sigma-Aldrich	Cat# A5441
Mouse anti-KRAS4B	Millipore Sigma	Cat# OP24
Rabbit anti-phospho-ERK1/2 T202/Y204	Cell Signaling Tech.	Cat# 4370
Rabbit anti-ERK1/2	Cell Signaling Tech.	Cat# 9102
Rabbit anti-phospho-AKT S473	Cell Signaling Tech.	Cat# 9271
Rabbit anti-AKT	Cell Signaling Tech.	Cat# 9272
Rabbit anti-phospho-p90RSK T359/S363	Cell Signaling Tech.	Cat# 9344
Rabbit anti-p90RSK	Cell Signaling Tech.	Cat# 9355
Rabbit anti-phospho-GSK3β S9	Cell Signaling Tech.	Cat# 5558
Rabbit anti-GSK3β	Cell Signaling Tech.	Cat# 12456
Species anti-phospho-MYC T58	Abcam	Cat# ab28842
Species anti-phospho-MYC S62	Abcam	Cat# ab106952
Rabbit anti-ubiquitin	Cell Signaling Tech.	Cat# 3933
Rabbit anti-phospho-ERK5 T218/T220	Cell Signaling Tech.	Cat# 3371
Rabbit anti-ERK5	Cell Signaling Tech.	Cat# 3372
Mouse anti-ERK5	Santa Cruz	Cat# sc-398015
Rabbit anti-phospho EGF receptor Y1068	Cell Signaling Tech.	Cat# 3777
Rabbit anti-EGF receptor	Cell Signaling Tech.	Cat# 4267
Rabbit anti-phospho-HER2/ErbB2 Y1248	Cell Signaling Tech.	Cat# 2247
Rabbit anti-HER2/Erbb2	Cell Signaling Tech.	Cat# 4290
Rabbit anti-phospho-Src Family Y416	Cell Signaling Tech.	Cat# 6943
Rabbit anti-Src	Cell Signaling Tech.	Cat# 2109
Rabbit anti-MEKK2	Cell Signaling Tech.	Cat# 19607
Rabbit anti-phospho-S6 Ribosomal Protein (Ser235/236)	Cell Signaling Tech.	Cat# 2211
Rabbit anti-cleaved Caspase-3 (Asp175)	Cell Signaling Tech.	Cat# 9661
Mouse anti-IgG	Santa Cruz	Cat# sc-2025
Rabbit anti-IgG	Cell Signaling Tech.	Cat# 2729
Species anti-MYC (IHC)	Abcam	Cat# ab32072
Species anti-phospho-ERK1/2 (IHC)	Cell Signaling Tech.	Cat# 4376
Species anti-phospho-AKT T308 (IHC)	Abcam	Cat# ab38449
Bacterial and Virus Strains
DH5α	Thermo Fisher	Cat# 18258012
Biological Samples
Chemicals, Peptides, and Recombinant Proteins
Doxycycline	Sigma-Aldrich	Cat# D3072
MG132	Sigma-Aldrich	Cat# M7449
Dimethyl sulfoxide	Fisher Scientific	Cat# BP231
Cycloheximide	Sigma-Aldrich	Cat# C4859
SCH772984	Merck	N/A
AZD6244	Astra-Zeneca	N/A
AZD5363	Astra-Zeneca	N/A
AZD8186	Astra-Zeneca	N/A
UNC10225170A	(Matossian et al., 2017)	N/A
XMD8–92 in vivo	MedChem Express	Cat# HY-14443
XMD8–92	Selleckchem	Cat# S7525
BIX02189	Selleckchem	Cat# S1531
Trametinib	Selleckchem	Cat# S2673
Poziotinib	Selleckchem	Cat# S7358
Erlotinib	Selleckchem	Cat# S1023
Saracatinib	Selleckchem	Cat# S1006
LY2874455	Selleckchem	Cat# S7057
Critical Commercial Assays
CellTiter-Blue Cell Viability Assay	Promega	Cat# G8081
XenoLight D-Luciferin - K+	Perkin Elmer	Cat# 122799
Doxycycline Diet (2020, 625 Dox, R)	Tekland	Cat# TD.130141
Deposited Data
N/A	N/A	N/A
Experimental Models: Cell Lines
INK4.1syn_Luc	(Collisson et al., 2012)	N/A
MIA PaCa-2	ATCC	Cat# CRL-1420
PANC-1	ATCC	Cat# CRL-1469
AsPC-1	ATCC	Cat# CRL-1682
Panc 10.05	ATCC	Cat# CRL-2547
HPAF-II	ATCC	Cat# CRL-1997
SW1990	ATCC	Cat# CRL-2172
Capan-2	ATCC	Cat# HTB-80
BxPC-3	ATCC	Cat# CRL-1687
Pa01C	(Jones et al., 2008)	N/A
Pa02C	(Jones et al., 2008)	N/A
Pa03C	(Jones et al., 2008)	N/A
Pa14C	(Jones et al., 2008)	N/A
Pa16C	(Jones et al., 2008)	N/A
Pa18C	(Jones et al., 2008)	N/A
HPAC	ATCC	Cat# CRL-2119
HPDE	(Radulovich et al., 2008)	N/A
HPDE-KRAS	(Radulovich et al., 2008)	N/A
HPNE	(Campbell et al., 2007)	N/A
HPNE-KRAS	(Campbell et al., 2007)	N/A
Experimental Models: Organisms/Strains
Mouse: FVB/n	The Jackson Laboratory	Cat# 001800
Mouse: NSG	The Jackson Laboratory	Cat# 005557
Mouse : NOD scid	The Jackson Laboratory	Cat# 001303
Oligonucleotides – See Table S2
Recombinant DNA
SMART	Dharmacon	V3SH7675
pMSCV MYC-FLAG	(Hayes et al., 2016)	N/A
pMSCV MYCT58A-FLAG	(Hayes et al., 2016)	N/A
pMSCV MYCS62A-FLAG	(Hayes et al., 2016)	N/A
pMSCV MYCT58/S62A-FLAG	(Hayes et al., 2016)	N/A
pGPS-LP	(Emanuele et al., 2011)	N/A
GPS-MYC	This paper	N/A
Kras (G12V)-pcw107	(Martz et al., 2014)	N/A
Hras (G12V)-pcw107	(Martz et al., 2014)	N/A
MEK1 (S218/222D)-pcw107	(Martz et al., 2014)	N/A
myr-FLAG-PIK3CA-pcw107	(Martz et al., 2014)	N/A
myr-FLAG-AKT1-pcw107	(Martz et al., 2014)	N/A
FLAG-Rheb1 (Q64L)-pcw107	(Martz et al., 2014)	N/A
beta-catenin (S33A/S37A/T41A)-pcw107	(Martz et al., 2014)	N/A
beta-catenin (S33Y)-pcw107	(Martz et al., 2014)	N/A
GSK3beta (K85A)-pcw107	(Martz et al., 2014)	N/A
JNK2 WT O/E (MAPK7)-pcw107-V5	(Martz et al., 2014)	N/A
FLAG-Mkk7-JNK2 fusion-pcw107	(Martz et al., 2014)	N/A
p38 WT O/E (MAPK14)-pcw107-V5	(Martz et al., 2014)	N/A
FLAG-MKK6 (S207/T211E)-pcw107	(Martz et al., 2014)	N/A
Notch1 intracellular domain-pcw107-V5	(Martz et al., 2014)	N/A
Notch3 intracellular domain-pcw107-V5	(Martz et al., 2014)	N/A
Myr-FLAG-MEK5	(Martz et al., 2014)	N/A
MEK5 DD(S311D/T315D)-pcw107-V5	(Martz et al., 2014)	N/A
myr-FLAG-MEK5-pcw107	(Martz et al., 2014)	N/A
HA-ERK5K84R	(Brady et al., 2014)	Addgene Cat# 53171
HA-ERK5 WT	(Brady et al., 2014)	Addgene Cat# 53175
HA-ERK5 WT	(Buschbeck et al., 2002)	Addgene Cat# 65244
HA-Ubiquitin	(Kamitani et al., 1997)	Addgene Cat# 18712
Software and Algorithms
GraphPad Prism 5 Software	GraphPad Software	N/A
SPSS Statistics	IBM	N/A
Summit 5.2	Beckman Coulter	N/A
Other
Multiplexed Kinase Inhibitor Beads (MIB)
A/G agarose beads	Santa Cruz Biotech.	Cat# sc-2003