Plasticity of hepatic cell differentiation: bipotential adult mouse liver clonal cell lines competent to differentiate in vitro and in vivo.

In fetal liver, bipotential hepatoblasts differentiate into hepatocytes and bile duct cells (cholangiocytes). The persistence of such progenitor cells in adult mouse liver is still debated. In damaged liver of adult murine animals, when hepatocyte proliferation is compromised, bipotential oval cells emerge, probably from bile ducts, proliferate, and differentiate to regenerate the liver.

Intracellular targeting of the type-I alpha regulatory subunit of cAMP-dependent protein kinase.

The specificity of cyclic adenosine monophosphate (cAMP)-mediated signaling events is achieved by the composition and biochemical properties of the different cAMP-dependent protein kinase holoenzymes (PKAI and II) and by compartmentalization of PKA to discrete subcellular locations. Intracellular localization is mediated by interaction with A-kinase anchoring proteins (AKAPs) that recruit PKAII close to its substrates and to sites where it can respond optimally to local changes in intracellular cAMP concentration, thereby directing and amplifying the effects of cAMP. This review presents recent evidence that indicates that specific AKAPs mediate PKAI anchoring through interaction with its regulatory subunit RI alpha, notably at the neuromuscular junction of skeletal muscle.

Muscle-regulated expression and determinants for neuromuscular junctional localization of the mouse RIalpha regulatory subunit of cAMP-dependent protein kinase.

In skeletal muscle, transcription of the gene encoding the mouse type Ialpha (RIalpha) subunit of the cAMP-dependent protein kinase is initiated from the alternative noncoding first exons 1a and 1b. Here, we report that activity of the promoter upstream of exon 1a (Pa) depends on two adjacent E boxes (E1 and E2) in NIH 3T3-transfected fibroblasts as well as in intact muscle. Both basal activity and MyoD transactivation of the Pa promoter require binding of the upstream stimulating factors (USF) to E1.

Type I protein kinase a is localized to interphase microtubules and strongly associated with the mitotic spindle.

We show here that type I protein kinase A is localized to microtubules during the entire cell cycle in epithelial (hepatoma, cervical carcinoma) and nonepithelial (myoblast) cell lines. The association of the type Ialpha regulatory subunit is very strong in all phases of mitosis, from prophase to cytokinesis. In interphase, the association appears weaker, reflecting perhaps a more dynamic molecular interaction.

Alternative 5'-exons of the mouse cAMP-dependent protein kinase subunit RIalpha gene are conserved and expressed in both a ubiquitous and tissue-restricted fashion.

The activity of cAMP-dependent protein kinase is controlled by its regulatory subunits. Mouse RIalpha regulatory subunit expression is initiated from five different non-coding 5'-regions (exons 1a, 1b, 1c, 1d and 1e). This organization appears to be conserved among species.