Hepatitis B “X” gene linked to cellular calcium release Leslie Lang  Gastroenterology  Volume 122, Issue 2, (February 2002) DOI: 10.1016/S0016-5085(02)80285-2 Copyright © 2002 American Gastroenterological Association Terms and Conditions

The HBV HBx protein possesses a number of activities, both nuclear and cytoplasmic, which include activation of signal-transduction pathways, stimulation of transcription, interaction with the proteasome, and activation of viral replication. As shown here, HBx activates cytoplasmic signal-transduction pathways by acting on mitochondria and/or the endoplasmic reticulum to alter the regulation of cytosolic calcium, which in turn activates the tyrosine kinase Pyk2. Pyk2 activates Src family tyrosine kinases in a calcium-dependent manner. Src kinases are activated by HBx, leading to downstream stimulation of other effector signal-transduction pathways such as Ras, the MAP kinases, and the JNK kinases. Activation of calcium release, Pyk2 and Src stimulate HBV reverse transcription and DNA replication through an unknown mechanism. Gastroenterology 2002 122, DOI: (10.1016/S0016-5085(02)80285-2) Copyright © 2002 American Gastroenterological Association Terms and Conditions