High impact information on Stk39

• The catalytic domain of SPAK contains an activation loop between the well-conserved DFG and APE motifs [1].
• Our recent studies demonstrate that SPAK (Ste20p-related Proline Alanine-rich Kinase), in combination with WNK4 [With No lysine (K) kinase], phosphorylates and stimulates the Na-K-2Cl cotransporter (NKCC1), whereas catalytically inactive SPAK (K104R) fails to activate the cotransporter [1].
• In this report, we demonstrate that coexpression of SPAK (T243A) or SPAK (T247A) with WNK4 not only prevented, but robustly inhibited, cotransporter activity in NKCC1-injected Xenopus laevis oocytes [1].
• In vitro phosphorylation experiments demonstrate that both intramolecular autophosphorylation of SPAK and phosphorylation of NKCC1 are significantly stronger in the presence of Mn2+ rather than Mg2+ [1].
• We also show that SPAK activity is markedly inhibited by staurosporine and K252a, partially inhibited by N-ethylmaleimide and diamide, and unaffected by arsenite [1].

Biological context of Stk39

• Based on the alignment of 12 sequences of protein motifs that interact with the kinases SPAK (Ste20-related proline alanine-rich kinase) and OSR1 (oxidative stress response 1), we performed genome-wide searches of the sequence [S/G/V]RFx[V/I]xx[V/I/T/S]xx, where x represents any amino acid [2].
• Induction of apoptosis by SLK, a Ste20-related kinase [3].

Anatomical context of Stk39

• In contrast, in choroid plexus epithelium from NKCC1 null mice, SPAK immunostaining was found in the cytoplasm [4].
• Immunohistochemical analysis of choroid plexus epithelium revealed co-expression of NKCC1 and SPAK on the apical membrane [4].

Associations of Stk39 with chemical compounds

• In the present study, we have demonstrated functional interaction between Ste20-related proline-alanine-rich kinase (SPAK), WNK4 [with no lysine (K)], and the widely expressed Na+-K+-2Cl- cotransporter type 1 (NKCC1) [5].

Analytical, diagnostic and therapeutic context of Stk39

• Evidence for in vivo interaction was established by co-immunoprecipitation of SPAK from mouse brain with anti-NKCC1 antibody [4].

References