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kinase activity is cytoplasmic in rat kidney (100 %), liver (94 0%) and heart (82 0%). whereas in cerebrum and testis most is particulate (88 % and 840%, respectively) [36].Immunological techniques have been used to demonstrate that in rat brain the subcellular distribution of the kinase, as well as its subunit composition, are under developmental control. The forebrain of 5-day postnatal rats contains approx. 800% cytoplasmic CaM-kinase II, with ax (50 kDa) and /3(60 kDa) subunits in a molar ratio of about 1:4 [37]. Between days 5 and 20 there is a 10fold increase in CaM-kinase II, with 80 % of the kinase now being particulate, and a 7: 1 ratio of a and , subunits [37]. The level of mRNA for the oc-subunit in forebrain also increases approx. 10-fold between postnatal days 1 and 21 [31]. In adult rat brain, the highest levels of CaMkinase II are found in the telencephalon regions (hippocampus, lateral septum, cortex, neostriatum, amygdaloid), with much lower activity in the cerebellum, diencephalon, mesencephalon, pons and medulla [9,38]. The ratio of subunits also varies between the different regions, with a and , subunits present in a 4: 1 ratio in rat forebrain and in a 1:4 ratio in cerebellum [12,39]. The variation in ratio of subunit polypeptides in these regions is paralleled by different ratios of the specific mRNA Vol. 258Abbreviations used: CaM-kinase II, Ca2+/calmodulin-dependent protein kinase II; cAMP-kinase, cyclic AMP-dependent protein kinase; protein kinase C, Ca2+/phospholipid-dependent protein kinase.* To whom correspondence and reprint requests should be addressed.Brain microtubule-associated proteins: MAP-2 and T. Microtubules are known to consist of tubulin and several microtubule-associated proteins or MAPs, some of which have been studied extensively. One of these, MAP-2, contains about 22 phosphorylation sites, 13 that are cyclic AMP-dependent and at least 8 that are cyclic AMP-independent [59]. MAP-2 is readily phosphorylated Vol. 258

The hepatitis C virus E1 and E2 envelope proteins are targeted to the endoplasmic reticulum, but instead of being secreted, they are retained in a pre-Golgi compartment, at least partly in a misfolded state. Since secretory proteins which are retained in the endoplasmic reticulum frequently can activate the transcription of intraluminal chaperone proteins, we measured the effect of the E1 and E2 proteins on the promoters of two such chaperones, GRP78 (BiP) and GRP94. We found that E2 but not E1 protein activates these two promoters, as assayed by a reporter gene system. Furthermore, E2 but not E1 protein induces the synthesis of GRP78 from the endogenous cellular gene. We also found that E2 but not E1 protein expressed in mammalian cells is bound tightly to GRP78. This association may explain the ability of E2 protein to activate transcription, since GRP78 has been postulated to be a sensor of stress in the endoplasmic reticulum. Since overexpression of GRP78 has been shown to decrease the sensitivity of cells to killing by cytotoxic T lymphocytes and to increase tumorigenicity and resistance to antitumor drugs, this activity of E2 protein may be involved in the pathogenesis of hepatitis C virus-induced diseases.

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