Table 1.

Comparison of existing biochemical data with proposed model predictions. Disruption of autoinhibition upon mutation of the indicated residues in conventional or novel PKC isozymes was determined experimentally either by assessing increased membrane translocation (11-13) or increased basal activity (18) in cells, or increased cofactor-independent activity of pure protein in vitro (22). Mutated residues were examined in the new structural model and predictions were made about inter- and intradomain interactions that may affect autoinhibition. Residues are numbered according to PKCβII.

Domain	Residue	Isozyme(s)	Disrupted Autoinhibition?	Prediction with New Model
C1A	R42	α	YES11	Interaction with E655 in C-Tail
	F43	α, βII,δ, η, θ	YES11,13	Interaction with F656, F659, or F661 in C-Tail
	T54	βII	NO13	No predicted interactions
	D55	α, βII	YES11,13	Interaction with R76, domain unfolding
	F72	α	YES11	interaction with F84, domain unfolding
C1B	T108	βII	NO13	No predicted interactions
	L125	βII	NO12*	Disrupt phorbol-binding pocket
C2	K236	βII	NO22	No predicted interactions
	R238	βII	NO22	No predicted interactions
Kinase	L358	α, βII, δ, η, θ	YES12,13	Could interact with Y422 or M145
	L367	βII	YES12	L367D could unfold N-lobe due to DE(D) negative patch
	D382	βII	YES18	Interaction with K91 (between C1A and C1B)
	Y422	βII	YES12	Could interact with L358 / in nucleotide binding region
	Y430	βII	YES12	Could pi-stack with H140 in C1B
C-Tail	F629	α, βII, δ, η, θ	YES12,13/NO18	No predicted interactions
	F633	α, βII, δ, η, θ	YES12,13	Could pi-stack with F114 in C1B
	E655	βII	YES18	Interaction with R42 in C1A

^*Phorbol-induced membrane translocation impaired