The serum- and glucocorticoid-induced kinase (SGK) is a serine-and threonine-kinase thought to be of importance for sodium reabsorption in the kidney. The epithelial sodium channel (ENaC), the Na⁺-K⁺-Cl^– cotransporter (NKCC), and the Na⁺,K⁺-ATPase increase their activity when co-expressed with SGK in epithelial cells or in Xenopus oocytes (Fillon et al. 2001). SGK is regulated at two different levels: transcription and activation of the protein by phosphorylation. A variety of stimuli have been shown to enhance transcription of the SGK gene, including serum, gluco- and mineralocorticoids, hypo- and hyperosmolarity and various growth factors. Activation of SGK depends on phosphorylation by 3-phosphoinositide-dependent kinases, PDK1 and PDK2 (Kobayashi & Cohen, 1999).

We have studied the expression and regulation of SGK in the mammalian kidney. Experiments were performed with a newly raised anti-SGK antibody on kidneys from rats with different levels of glucocorticoids and/or mineralocorticoids. Adrenalectomy and dexamethasone replacement were performed as previously described (Stanton et al. 1985). Rats were anaesthetized by ether inhalation for surgical preparations. After each treatment rats were anaesthetized by pentobarbital (100 mg per 100 g body weight) and the kidneys were processed for Western blotting or fixed and processed for immunohistochemistry.

The results indicate that SGK expression is restricted to the thick ascending limb (TAL), the distal convoluted (DCT) and cortical collecting tubules (CCT). The distribution of SGK does not correspond to the classical aldosterone-responsive tubule segments. Within cells, SGK localizes to the basolateral plasma membrane in close proximity with the Na⁺,K⁺-ATPase. Differential centrifugation and Western blotting further confirmed the association of SGK with membranes. Kidneys from control animals express high levels of SGK protein, which are not significantly affected by physiological increases in aldosterone. Adrenalectomy reduces SGK protein expression by 40 % (± 0.07, P < 0.001, Student’s paired t test) and dexamethasone replacement restores SGK levels back to normal.

The constitutive expression of SGK in the TAL, DCT and CCT suggests a permissive effect of the kinase on the activity of ion channels and transporters expressed in these segments of the tubule. The Na⁺,K⁺-ATPase is the only target that could directly interact with SGK. However, a unifying model for SGK action would require intermediaries to transmit the effects of SGK to proteins located in both the apical and basolateral membranes.

This work was supported by an NIH grant to C.M.C. and the National Kidney Foundation to D.A.R.