期刊
出版社
BLACKWELL PUBLISHING
DOI: 10.1111/j.1749-6632.2009.04054.x
关键词
tight junction; occludin; protein kinase; protein phosphatase; ZO-1; epithelium; barrier function; PKC; PP2A; Src
资金
- NIAAA NIH HHS [AA12307, R01 AA012307] Funding Source: Medline
- NIDDK NIH HHS [R01 DK055532, R56 DK055532, DK55532] Funding Source: Medline
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK055532, R56DK055532] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM [R01AA012307] Funding Source: NIH RePORTER
Occludin is the first transmembrane protein of the tight junction to be discovered. While numerous studies emphasized the important role of occludin in assembly and maintenance of tight junctions, occludin knockout studies indicated that it was not required for tight junction assembly in different epithelia. However, a detailed characterization of the occludin knockout mouse concluded that the occludin gene is indispensable, and plays a complex role in regulation of epithelial tight junctions in different organs. This article describes the role of occludin phosphorylation in the regulation of its assembly into the tight junctions. Occludin is highly phosphorylated on Ser and Thr residues, while Tyr-phosphorylation is kept at minimum in the intact epithelium. During the disruption of tight junctions by various factors, occludin undergoes dephosphorylation on Ser/Thr residues and elevated phosphorylation on Tyr residues. The phosphorylation of occludin on Tyr, Ser, and Thr residues appears to be regulated by the balance between protein kinases such as c-Src, PKC zeta, and PKC lambda/L, and protein phosphatases such as PP2A, PP1, and PTP1B. The precise mechanism of regulation of the tight junction by occludin phosphorylation is unclear at this time. However, an in vitro study indicated that Tyr-phosphorylation of occludin C-terminal domain attenuates its interaction with ZO-1. Therefore, phosphorylation of specific Ser/Thr/Tyr residues in occludin may regulate its interactions with ZO-1 and possibly other tight junction proteins. It is likely that occludin plays a regulatory role in tight junctions rather than a role in the de novo assembly of tight junctions.
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