Table 2.

Different enzymes involved in phosphorylation and dephosphorylation of NKCC1

Sr. No.	Kinases/ Phosphatase Enzyme	Phosphorylation/ Dephosphorylation Site	Comment	Reference
1.	Ca2+/Camodulin-kinase-II	NKCC1 phosphorylation	Capsaicin induces NKCC1 phosphorylation due to stimulation of Ca2+/Camodulin-kinase-II in the mouse spinal cord	Galena and Cervero, 2005
2.	Protein kinase A	NKCC1 phosphorylation	protein kinase A is involved in NKCC1 phosphorylation in rat acinar basolateral membranes by activation of endogenous membrane-associated kinases or inhibition of phosphatases present in acinar basolateral membranes	Khurihara et al., 2002
3.	Protein phosphatase type 1	NKCC1 dephosphorylation	Protein phosphatase type 1 enzyme binds to the NKCC1 via RVXFXD sequence present in N-terminus sites of regulatory subunit to promote dephosphorylation and inactivation of NKCC1	Darman et al.,2001; Matskevich et al., 2005
4.	Protein kinase C	NKCC1 phosphorylation	Protein kinase C may activate Ste20-related proline-alanine-rich kinase (SPAK), which subsequently binds to the N-terminal of NKCC1 and causes its phosphorylation during hyperosmotic stress in human airway epithelial cells	Dowd and Forbush, 2003; Smith et al., 2008
5.	With No K=lysine kinases (WNK) WNK1, WNK2 and WNK3 WNK4	NKCC1 phosphorylation NKCC1 phosphorylation NKCC1 phosphorylation	With No K=lysine kinases (WNK) phosphorylates and activates Ste20-related proline/alanine-rich kinase/Oxidative stress responsive kinases (SPAK/OSR1) that subsequently regulate phosphorylation and activation of NKCC WNK1, WNK2 and WNK3 auto-phosphorylates their Thr243, Ser382, Ser383, Ser1261 residues in response to stress and activated SPAK/OSR1 regulates the phosphorylation of Thr203, Thr207 and Thr212 residues of NKCC WNK4 in association withcalcium binding protein 39 (cbp39) may alsoactivate NKCC1 in a SPAK/OSR1-independent manner	Susa et al., 2012; Zeniya et al., 2013 Thastrup et al., 2012 Gagnon et al., 2011; Ponce-Coria et al., 2014