. 2011 Jun 28;3(3):107. doi: 10.1007/s12551-011-0050-y

Table 1.

Summary of the individual protein kinase C phosphorylation sites on all myofilament proteins^a

Myofilament protein	PKC phospho-site	Primary or secondary PKC site	PKC isoform	Effect on the myofilament properties of the heart
MLC-2	Ser15	Secondary	Isoform unknown	- Phosphorylation of MLC-2 by PKC increased the maximal Ca²⁺-stimulated MgATPase activity without altering the Ca²⁺-sensitivity in cardiac rat whole myosin (Noland and Kuo 1993).
cTnI	Ser23/24	Secondary	-PKCδ, PKCα, PKCβ, PKCδ	- PKCδ phosphorylation of bovine cTn complex decreased Ca²⁺-sensitivity of actomyosin S-1 MgATPase (Jideama et al. 1996).
			-PKCβII, PKCε	- PKCδ-dependent phosphorylation decreased force development at submaximal Ca ²⁺ in skinned rat cardiomyocytes (Sumandea et al. 2008).
				- Phospho mimicked Ser23/24 causes a decreased Ca²⁺-sensitivity (Lu et al. 2010).
	Ser43/45	Primary	- PKCδ	- PKCδ and PKCα phosphorylation of bovine cTn complex reduced maximal activity of MgATPase (Jideama et al. 1996).
			- PKCα	- TG mice harboring unphosphorylatable sites showed systolic and diastolic lower intracellular Ca²⁺ and prolonged duration of Ca²⁺ transient (MacGowan et al. 2004).
				- Papillary muscles from TG mice harboring unphosphorylatable alanines showed decreased maximal force upon α-adrenergic stimulation (Montgomery et al. 2002).
				- Phosphorylation mimicking reduces the maximal force of tension in skinned fibers from mice and in vitro motility assays (Burkart et al. 2003).
				- TG mice overexpressing PKCε and harboring non-phosphorylatable Ser43 and 45 sites showed less declination in LV function compared to the PKCε mice, indicating that PKCε phosphorylation of Ser43 and 45 plays a prominent role in depressing contractility in normal, healthy mice (Scruggs et al. 2006).
				- Skinned fibers from mice harboring alanines at sites 43 and 45 showed deceased maximal tension and increased MgATPase activity. PKC activation increased maximum tension and stiffness (Pyle et al. 2006).
	Ser76(77)	Unknown	Isoform unknown	- No data available on site specific function (Zabrouskov et al. 2008).
	Thr143	Primary	-PKCβII	- PKCβII showed a phosphorylation preference for Thr144 and showed a decreased Ca²⁺ -sensitivity of force in skinned myocytes from TG mice (Wang et al. 2006).
			-PKCδ	- Phosphorylation mimicked Thr143 causes a depression of Hill coefficient in the presence of Ser23/24 phospho in skinned mice muscle fibers (Lu et al. 2010).
				- cTnI Thr143 In rat skinned trabeculae modulates length-dependent activation (Tachampa et al. 2007).
				- Alanine substitution of Thr143 in reconstituted thin filaments showed involvement in NEM-S1-dependent activation of ATPase activity in the absence of Ca²⁺ (Kobayashi et al. 2009).
cTnT	Ser1	Primary	Isoform unknown	- No data available on site specific function (Sancho Solis et al. 2008)
	Ser198	Primary	Unknown	- No functional effects measured (Sumandea et al. 2003).
	Thr194	Primary	Isoform unknown	- No functional effects measured (Sumandea et al. 2003).
	Thr203	Primary	PKCα	- Phospho mimicking in mice resulted in decreased maximal tension, actomyosin Mg-ATPase activity, Ca²⁺-sensitivity and cooperativity (Sumandea et al. 2003)
	Thr284	Primary	Unknown	- No functional effects measured (Sumandea et al. 2003)
MyBP-C	Ser304	Secondary	PKCε	- PKCε overexpressing mice developed dilated cardiomyopathy at 9–12 months of age (Xiao et al. 2007).
	Ser304	Secondary		- TG mice with alanine substitution of phosphorylation sites displayed depressed cardiac contractility and altered sarcomeric structure (Sakthivel et al. 2005).
	Ser275	Secondary	Isoform unknown	- TG mice with alanine substitution of phosphorylation sites displayed depressed cardiac contractility and altered sarcomeric structure (Sakthivel et al. 2005).
Titin	Ser11878/ 12022	Primary	PKCα	- PKCα phosphorylation increases passive force (Hidalgo et al. 2009)

PKC, Protein kinase; MLC-2, myosin light chain-2; cTnl, cardiac troponin I; cTnT, cardiac troponin T; MyBP-C, myosin binding protein-C

The table lists whether the sites are primary or secondary substrates for protein kinase C (PKC)-mediated phosphorylation and the site specificity of the different PKC isoforms (as far as known). The function of the individual sites are described and their role in the propensity towards heart failure. The myofilament protein desmin has not been included in the table since, to the best of our knowledge; there is no site-specific information available for desmin