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PKC and ERK1/2 regulate amylase promoter activity during differentiation of a salivary gland cell line
Author(s) -
Jung Dale W.,
Hecht Dalit,
Ho Susan W.,
O'Connell Brian C.,
Kleinman Hynda K.,
Hoffman Matthew P.
Publication year - 2000
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/1097-4652(200011)185:2<215::aid-jcp6>3.0.co;2-l
Subject(s) - rottlerin , protein kinase c , biology , signal transduction , thapsigargin , microbiology and biotechnology , cell culture , tetradecanoylphorbol acetate , phosphorylation , matrigel , chemistry , extracellular , genetics
The addition of transforming growth factor α (TGFα) to a human submandibular gland cell line (HSG) cultured on basement membrane extract Matrigel, synergistically activates the acinar cell–specific salivary amylase promoter. Signaling through β1 integrins and increased phosphorylation of ERK1/2 are involved in the increased promoter activity. Phorbol‐12‐myristate‐13‐acetate (PMA) and thapsigargin increase amylase promoter activity, suggesting that phorbol ester and calcium‐dependent protein kinase C (PKC) pathways are also involved. The combination of specific inhibitors of PKC and MEK1 inhibits the amylase promoter. Inhibitors of the calcium‐dependent PKC isoforms α, β, and γ decrease the promoter activity; however, PKCβ is not detectable in HSG cells. TGFα alters the cellular localization of PKCα but not ‐γ, suggesting PKCα is involved in TGFα upregulation of the amylase promoter. Furthermore, rottlerin, a PKCδ‐specific inhibitor, increases the promoter activity, suggesting PKC isoforms differentially regulate the amylase promoter. In conclusion, β1‐integrin and TGFα signaling pathways regulate the amylase promoter activity in HSG cells. In response to Matrigel and TGFα, the activation of both PKCα and phosphorylation of ERK1/2 results in synergistic activation of the amylase promoter. J. Cell. Physiol. 185:215–225, 2000. Published 2000 Wiley‐Liss, Inc.