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Caveolin‐1 Phosphorylation by Src Kinase Regulates Epithelial Restitution by Altering Store‐Operated Ca 2+ Influx
Author(s) -
Rao Jaladanki N,
Rathor Navneeta,
Zhuang Ran,
Zou Tongtong,
Liu Lan,
Xiao Lan,
Wang Jian-Ying
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1157.3
Subject(s) - proto oncogene tyrosine protein kinase src , phosphorylation , caveolin 1 , microbiology and biotechnology , restitution , chemistry , kinase , cell migration , cell , biochemistry , biology , political science , law
Early mucosal restitution occurs as a consequence of intestinal epithelial cell (IEC) migration to reseal superficial wounds. Our previous study shows that caveolin‐1 (Cav1) enhances store‐operated Ca 2+ entry (SOCE) and is implicated in the control of intestinal epithelial restitution, but the exact mechanism by which Cav1 activity is regulated remains elusive. This study determine if c‐Src kinase modulates Cav1, thus activating Cav1‐mediated SOCE after wounding. [Ca 2+ ] cyt , Cav1/c‐Src interaction, and restitution were measured in differentiated IEC cells. c‐Src directly interacted with and phosphorylated Cav1 in IECs. Inhibition of c‐Src activity by PP2 prevented c‐Src/Cav1 interaction, reduced Cav1 phosphorylation, decreased Ca 2+ influx after store depletion, and inhibited cell migration after wounding. Disruption of caveolar lipid raft microdomains by methyl‐β‐cyclodextrin (MβCD) or by blocking a functional caveolin‐scaffolding domain with CSD decreased Cav1/c‐Src association, reduced Cav1 phosphorylation and SOCE, and repressed epithelial restitution. The levels of SOCE were inhibited by ~65% and ~80% after treatment with MβCD and CSD peptides, respectively, and cell migration was decreased by ~40%. These results indicate that 1) c‐Src phosphorylates Cav1 and activates its activity 2) c‐ Src‐mediated Cav1 stimulates epithelial restitution by increasing Ca 2+ signaling. Grants: NIH/VA