title: Increased nuclear translocation of catalytically active PKC-zeta during mouse colonocyte hyperproliferation.
abstract: Protein kinase (PK) C-zeta is implicated in the control of colonic epithelial cell proliferation in vitro. However, less is known about its physiological role in vivo. Using the transmissible murine colonic hyperplasia (TMCH) model, we determined its expression, subcellular localization, and kinase activity during native crypt hyperproliferation. Enhanced mitosis was associated with increased cellular 72-kDa holoenzyme (PKC-zeta, 3.2-fold), 48-kDa catalytic subunit (PKM-zeta, 3- to 9-fold), and 24-kDa membrane-bound fragment (M(f)-zeta, >10-fold) expression. Both PKC-zeta and PKM-zeta exhibited intrinsic kinase activity, and substrate phosphorylation increased 4.5-fold. No change in cellular PKC-iota/PKM-iota expression occurred. The subcellular distribution of immunoreactive PKC-zeta changed significantly: neck cells lost their basal subcellular pole filamentous staining, whereas proliferating cell nuclear antigen-positive cells exhibited elevated cytoplasmic, lateral membrane, and nuclear staining. Subcellular fractionation revealed increased PKC-zeta and PKM-zeta expression and activity within nuclei, which preferentially accumulated PKM-zeta. These results suggest separate cellular and nuclear roles, respectively, for PKC-zeta in quiescent and mitotically active colonocytes. PKM-zeta may specifically act as a modulator of proliferation during TMCH.
authors.affiliation: Department of Integrative Biology, Pharmacology, and Physiology, University of Texas Health Science Center at Houston, Medical School, 77030, USA.
authors.forename: S
authors.initials: S
authors.lastname: Umar
authors.forename: J H
authors.initials: JH
authors.lastname: Sellin
authors.forename: A P
authors.initials: AP
authors.lastname: Morris
mesh_terms: D000818:Animals; D000906:Antibodies; D015153:Blotting, Western; D020134:Catalytic Domain / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002467:Cell Nucleus / Q000201:enzymology*; D002954:Citrobacter; D003106:Colon / Q000201:enzymology* / Q000382:microbiology / Q000473:pathology*; D003600:Cytosol / Q000201:enzymology; D004756:Enterobacteriaceae Infections / Q000201:enzymology / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D006965:Hyperplasia; D007413:Intestinal Mucosa / Q000201:enzymology / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D000099221:Protein Kinase C zeta
chemical_list: D000906:Antibodies; D011493:Protein Kinase C; D000099221:Protein Kinase C zeta