Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Double-stranded RNA (dsRNA)-dependent protein kinase (p68) has been shown to be induced by alpha-interferon (IFN-alpha) in mammalian cells. It binds to dsRNA, and is believed to be a factor in the control of both cellular and viral protein synthesis. This report describes the use of a new monoclonal antibody (MAb) TJ4C4, to monitor levels of p68 in a patient with AIDS-associated Kaposi's sarcoma. Using a novel immunoperoxidase/iron staining method, we examined formalin-fixed, paraffin-embedded biopsies prior to, and 4 months after the initiation of IFN therapy. Immunostaining showed low levels (1+ staining) of p68 in the pretreatment tissue, whereas a marked increase (4+ staining) was noted during interferon treatment. This staining suggests an increased level of intracellular p68 expression. This patient has subsequently remained on IFN-alpha therapy and is alive with no evidence of Kaposi's sarcoma, 6 1/2 years after diagnosis. The use of MAb TJ4C4 will greatly facilitate the study of p68 kinase in clinical tissues, and may provide a way to monitor the effects of IFN therapy.
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PMID:Immunohistochemical detection of double-stranded-RNA-dependent protein kinase (p68) with a novel monoclonal antibody TJ4C4. A case report of an AIDS-associated Kaposi's sarcoma treated with alpha-interferon. 128 28

Reactivation of Kaposi's sarcoma-associated herpesvirus (KSHV) lytic replication is mediated by the viral RTA transcription factor, but little is known about the physiological processes controlling its expression or activity. Links between autonomic nervous system activity and AIDS-associated Kaposi's sarcoma led us to examine the potential influence of catecholamine neurotransmitters. Physiological concentrations of epinephrine and norepinephrine efficiently reactivated lytic replication of KSHV in latently infected primary effusion lymphoma cells via beta-adrenergic activation of the cellular cyclic AMP/protein kinase A (PKA) signaling pathway. Effects were blocked by PKA antagonists and mimicked by pharmacological and physiological PKA activators (prostaglandin E2 and histamine) or overexpression of the PKA catalytic subunit. PKA up-regulated RTA gene expression, enhanced activity of the RTA promoter, and posttranslationally enhanced RTA's trans-activating capacity for its own promoter and heterologous lytic promoters (e.g., the viral PAN gene). Mutation of predicted phosphorylation targets at RTA serines 525 and 526 inhibited PKA-mediated enhancement of RTA trans-activating capacity. Given the high catecholamine levels at sites of KSHV latency such as the vasculature and lymphoid organs, these data suggest that beta-adrenergic control of RTA might constitute a significant physiological regulator of KSHV lytic replication. These findings also suggest novel therapeutic strategies for controlling the activity of this oncogenic gammaherpesvirus in vivo.
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PMID:beta-Adrenoreceptors reactivate Kaposi's sarcoma-associated herpesvirus lytic replication via PKA-dependent control of viral RTA. 1622 74