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World Journal of Gastrointestinal Pathophysiology

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WW<br />

sequence<br />

N<br />

PKC<br />

Tyrosine<br />

Kinase c-Yes<br />

PI3K<br />

CK2<br />

PP2A<br />

First extracellular loop Second extracellular loop<br />

cient mice �9� presented abnormalities from several tissues<br />

e.g., chronic inflammation and hyperplasia <strong>of</strong> the gastric<br />

epithelium, calcification in the brain, testicular atrophy,<br />

thinning <strong>of</strong> the compact bone and loss <strong>of</strong> cytoplasmic<br />

granules in striated duct cells <strong>of</strong> the salivary glands.<br />

Furuse et al �10� identified the first two members <strong>of</strong> the<br />

claudin superfamily, claudins 1 and 2. Comparing their<br />

WJGP|www.wjgnet.com<br />

C<br />

ZO-1 ZO-2 ZO-3 F-actin<br />

Connexins 32 and 26<br />

Long carboxyterminal tail<br />

150 aa sequence<br />

a helix<br />

Figure 1 Occludin. WW sequences are highly preserved 35-45 aminoacid segments, containing Trp and Pro. They recognize proline rich domains. Ser 379 and Thr<br />

375 are casein kinase 2 (CK2) phosphorylation sites. PKC: Protein kinase C; PI3K: Phosphatidylinositol 3 kinase; PP2A: Protein phosphatase 2A; ZO: Zonula occludens.<br />

Homophilic<br />

reaction<br />

Enterotoxins<br />

Claudins<br />

Hoterophilic<br />

reaction<br />

Hoteropolymers<br />

First extracellular loop<br />

�hydrophobic��<br />

cell to cell contact<br />

Second extracellular<br />

loop selective ionic<br />

channels<br />

ZO-1<br />

ZO-2<br />

Homopolymers C<br />

Figure 2 Claudin(s). PKC: Protein kinase C; CK2: Casein kinase 2; ZO: Zonula occludens.<br />

N<br />

ZO-3<br />

Assimakopoulos SF et al . Enterocytes’ T�s<br />

Thr 375<br />

Ser 379<br />

PKC<br />

CK2<br />

cA�P dependent<br />

kinase<br />

sequence to already known proteins, they found similarity<br />

to at least three membrane-associated proteins: rat ventral<br />

prostate-1, clostridium perfringens enterotoxin receptor<br />

and oligodendrocyte specific protein �11� . Up until now, the<br />

claudin family consists <strong>of</strong> 24 members in humans �12,13�<br />

�Table 1�.<br />

Claudins are transmembrane proteins with MW rang-<br />

125 December 15, 2011|Volume 2|Issue 6|

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