| Control Peptide for W2996-02 (antiserum) and W2996-01 (affinity purified) A 17-aa peptide sequence, mapping near the N-terminus and prior to the tyrosine kinase catalytic domain of human WNK-1 . Protein kinases represent a superfamily of over 400 members that share a catalytic domain of 250-300 amino acids. A conserved lysine, in subdomain II of the catalytic core of all 390 protein kinases, anchors a and b phosphoryl groups of ATP. The catalytic domain of WNK (With No K=Lysine) kinases contains all invariant residues, except for this lysine residue. There are 4 (identified) WNK genes (WNK1, WNK2, WNK3 and WNK4) in human (h) and rat (r). The hWNK kinases exhibit ~30% seq identity and 50% seq homology to human Mitogen Activated Protein kinases (MAPK) STK2, PAK2, MEKK3, PAK3 and Raf-1. The mutation in genes expressing WNK1 (chromosome 12p13.3) and WNK4 (chromosome 17q) causes Pseudohypoaldosteronism type II (PHAII), an autosomal disorder featuring hypertension, hyperkalemia (high serum K+ level), normal/elevated aldosterone level, increased renal salt absorption, and impaired K+ and H+ excretion. WNK1 (251kD, 2382aa, chromosome 12p13.3) is a serine-threonine kinase in which the conserved catalytic lysine in subdomain II is replaced by a cystine but another lysine residue in subdomain I confers the kinase activity. The hWNK1 is ~86% identical to rat WNK1(230kD, 2126aa). The two transcripts of hWNK1 (8.5 and 10 kb) enzyme are expressed in most tissues but predominantly in kidney, heart and muscle and weakly in brain. In cells of these tissues, WNK1 is present throughout the cytoplasm. WNK1 localizes to the distal convoluted tubule (DCT), medullary and cortical collecting ducts (MCD and CCD), adjacent segments of the distal nephron that play a key role in salt, water, K+ and pH homeostasis. In the CD, Na+ is reabsorbed by the epithelial sodium channel (ENaC) providing the electrical diving force for K+ and H+ secretion. Considering the PHAII-features, WNK1 possibly, increases the transcellular or paracellular Cl- conductance in CD, thereby increasing salt reabsorption and intravascular volume, while concomitantly dissipating the electrical gradient and diminishing K+ and H+ secretion. Storage and Stability: Lyophilized powder may be stored at -20C. Stable for 12 months at -20C. Reconstitute with sterile buffer or ddH2O. Aliquot to avoid repeated freezing and thawing. Store at -20C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer. |
