Interleukin-2 (IL-2) signaling requires the dimerization of the IL-2 receptor beta.(IL-2R beta) and common gamma (gamma c) chains. Mutations of gamma c can result in X-linked severe combined immunodeficiency (XSCID). IL-2, IL-4, IL-7 (whose receptors are known to contain gamma c), and IL-9 (whose receptor is shown here to contain gamma c) induced the tyrosine phosphorylation and activation of the Janus family tyrosine kinases Jak1 and Jak3. Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively; IL-2 induced Jak3-IL-2R beta and increased Jak3-gamma c associations. Truncations of gamma c, and a gamma c, point mutation causing moderate X-linked combined immunodeficiency (XCID), decreased gamma c-Jak3 association. Thus, gamma c mutations in at least some XSCID and XCID patients prevent normal Jak3 activation, suggesting that mutations of Jak3 may result in an XSCID-like phenotype.

Interleukin-2 is an autocrine growth factor for T cells which also activates other cells including B cells and natural killer cells. The subunits of the interleukin-2 receptor (IL-2R) lack intrinsic enzymatic activity, but protein tyrosine phosphorylation is a critical event following ligand binding and src family kinases, such as Lck, are known to be activated by IL-2 (refs 5-9). However, IL-2 signalling can occur in the absence of receptor interaction with Lck, suggesting that other protein tyrosine kinases might be important. Here we report that a new member of the Janus family of kinases (Jak-3) is coupled to the IL-2R in human peripheral blood T cells and natural killer cells.

Protein-tyrosine kinases (PTKs) (5,6,(22)(23)(24)(25). Recently, an additional family ofPTKs, the Janus family ofkinases (JAKs), has been described. These kinases, JAK1, JAK2, and Tyk2, are structurally quite distinct in that they possess tandem nonidentical catalytic domains (26-29). These PTKs have also been shown to be involved in signaling by a number of cytokine and hormone receptors (30-36). These family members are also of interest in that they appear to exert their effect through tyrosine-phosphorylated transcription factors (37,38

Cochlear endolymph has a highly positive potential of approximately +80 mV. This so-called endocochlear potential (EP) is essential for hearing. Although pivotal roles of K+channels in the formation of EP have been suggested, the types and distribution of K+channels in cochlea have not been characterized. Because EP was depressed by vascular perfusion of Ba2+, an inhibitor of inwardly rectifying K+(Kir) channels, but not by either 4-aminopyridine or tetraethylammonium, we examined the expression of Kir channel subunits in cochlear stria vascularis, the tissue that is supposed to play the central role in the generation of positive EP. Of 11 members of the Kir channel family examined with reverse transcription-PCR, we could detect only expression of KAB-2 (Kir4.1) mRNA in stria vascularis. KAB-2 immunoreactivity was specifically localized at the basolateral membrane of marginal cells but not in either basal or intermediate cells. Developmental expression of KAB-2 in marginal cells paralleled formation of EP. Furthermore, deaf mutant mice (viable dominant spotting; WV/WV) expressed no KAB-2 in their marginal cells. These results suggest that KAB-2 in marginal cells may be critically involved in the generation of positive EP.

Sodium- and potassium-dependent ATPase [(Na+ + K+)ATPase], which is responsible for the active transport of Na+ and K+, is distributed universally among animal cell membranes and consists of two types of subunits, alpha and beta (refs 1-4). The larger alpha-subunit with a relative molecular mass (Mr) of 84,000-120,000 is thought to have the catalytic role. We have now cloned and sequenced DNA complementary to the Torpedo californica electroplax messenger RNA encoding the alpha-subunit of (Na+ + K+)ATPase and have deduced the complete amino-acid sequence of the polypeptide. Some structural features of the alpha-subunit molecule related to the function of this active-transport protein are discussed.

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Xenopus oocytes injected with s(-and /?-subunit-specific mRNAs derived from cloned Torpedo californica cDNAs. Both the mRNAs are required for the expression of functional (Na+ + K+)-ATPase.