Table 1. Genetically Encoded ERK activity Biosensors grouped based on their sensing modality.

Reporter Type	Reporter name (aliases)	Subcellular Resolution of ERK activity	Dynamic Range	Response Time (approx.)	Sensitivity	Fluorescent Protein(s)	Cell Shape Sensitivity	CDK Sensitivity	Reference
FP-fused ERK	FP-ERK (BFP-ERK, (GFP-ERK)	No	+	3min	+	BFP, GFP *	Yes	No	[52,79,185]
Degron	FIRE	No	+++	150 min	+++	mVenus *	No	No	[31]
Kinase Translocation Reporter (KTR)	ERK-KTR (ERKKTR, ERKTR)	No	++++	3 min	+++	Clover *	Yes	Yes	[3]
Forster Resonance Energy Transfer (FRET)	EKAR	Yes	+	1 min	++	mVenus, mCerulean	No	Yes	[27]
	EKAREV (EKARev, EKAR-EV)	Yes	++	1 min	++	YPet, ECFP	No	Yes	[181]
	EKAR2G1	Yes	+	1 min	+	cp173Venus, cp227mTFP1	No	Yes	[182]
	EKAR-TVV	Yes	++	1 min	++	cp173Venus-Venus, mTurquoise	No	Yes	[53,182]
	RAB- EKARev	Yes	++	5 min	NA	ddRFP-A, ddRFP-B	No	Unknown	[183]
	FPX-EKAR	Yes	+ (50% of EKARev)	5 min	+	Red-ddFP, Green-ddFP, ddFP (B)	No	Unknown	[184]
	EKAR3	Yes	+	1 min	++	YPet, mTurquoise2	No	Yes	[50]
	EKAR4	Yes	+++	1 min	++	ECFP, YPet	No	No	[36]
	EKAR-EN4 (EKAREN4)	Yes	+++	1 min	++	ECFP, YPet	No	No	[48]
	EKAR-EN5 (EKAREN5)	Yes	+++	1 min	+++	YPet, mTurquoise2	No	No	[48]

Fluorescent protein fused ERK (FP-ERK) translocates partially to the nucleus when phosphorylated by MEK allowing average cellular activity to be estimated by the nuclear to cytosolic fluorescence ratio. The Degron reporter (FIRE) is stabilized upon phosphorylation by ERK such that its fluorescence indicates ERK activity on a scale of 3-12 hours. Upon phosphorylation, KTR reporters shift in their preference for nuclear import vs. export allowing their nuclear vs. cytosolic ratio to reflect the average cellular ERK activity on the scale of minutes. FRET reporters shift in conformation upon phosphorylation by ERK allowing the ratio of fluorescent protein intensities to reflect subcellular ERK activity on the scale of minutes. Subcellular resolution of ERK activity: yes indicates the capability for the reporter to be localized to different subcellular compartments and to therefore reflect the activity of a specific region. Response Time: an estimate of time from ERK activation to apparent localization/fluorescence change. Cell Shape Sensitivity: the apparent read-out of translocation-based reporters can be shifted independently of ERK by changes in cell shape. Cyclin Dependent Kinase (CDK) sensitivity: Some reporters can be phosphorylated independently of ERK by Cyclin Dependent Kinases. * any fluorescent protein can be theoretically used.