Figure 2.

Structural and functional domains of cardiac TnI and posttranslational modifications. Indicated on this linear map of cardiac TnI polypeptide (residue # corresponds to that in human sequence including Met1), Ser₂₃/Ser₂₄ are phosphorylated by PKA (Solaro and Kobayashi, 2011), decreasing Ca²⁺ sensitivity and accelerating relaxation. They have also been reported to be phosphorylated by PKC-β, PKC-ε (Kobayashi et al., 2005), PKD (Haworth et al., 2004; Cuello et al., 2007; Bardswell et al., 2010) and PKG (Layland et al., 2002). Ser₄₂/Ser₄₄, Thr₁₄₃, and Ser₁₅₀ are phosphorylated by PKC, Pak or AMPK, decreasing Ca²⁺ sensitivity and slowing relaxation (Macgowan et al., 2001; Buscemi et al., 2002; Pi et al., 2002; Burkart et al., 2003b; Westfall et al., 2005). Thr₃₁ and Thr₅₁ are phosphorylated by Mst1 (You et al., 2009) with unknown function. New phosphorylation sites have been identified in the N-terminal region (Ser₅/Ser₆, with decreased levels in heart failure) and in the C-terminal region (Ser₁₆₆/Thr₁₈₁/Ser₁₉₉, with unknown kinases and functions) (Zhang et al., 2012). A restrictive N-terminal truncation of cardiac TnI occurs in adaptation to hemodynamic stresses to selectively remove the adult heart-specific N-terminal extension with an effect on increasing myocardial relaxation, similar to the effect of PKA phosphorylation at Ser₂₃/Ser₂₄ (Barbato et al., 2005). A deletion of the C-terminal 19 amino acids was found in myocardial ischemia-reperfusion injury (McDonough et al., 1999) and myocardial stunning (McDonough et al., 2001), slowing down the rates of force development and relaxation (Narolska et al., 2006).