p11, a Unique Member of the S100 Family of Calcium-binding Proteins, Interacts with and Inhibits the Activity of the 85-kDa Cytosolic Phospholipase A2

Abstract

Using a two hybrid system screen of a human cDNA library, we have found that p11, a unique member of the S100 family of calcium-binding proteins, interacts with the carboxyl region of the 85-kDa cytosolic phospholipase A 2 (cPLA 2 ). p11 synthesized in a cell-free system interacts with cPLA 2 in vitro. The p11-cPLA 2 complex is detectable from a human bronchial epithelial cell line (BEAS 2B). Furthermore, p11 inhibits cPLA 2 activity in vitro. Selective inhibition of p11 expression in the BEAS 2B cells by antisense RNA results in an increased PLA 2 activity as well as an increased release of prelabeled arachidonic acid. This study demonstrates a novel mechanism for the regulation of cPLA 2 by an S100 protein.

N‐terminal and C‐terminal plasma membrane anchoring modulate differently agonist‐induced activation of cytosolic phospholipase A2

“…The protein p11, a member of S100 family proteins, forms a heterotetrameric annexin II 2 p11 2 complex that is concentrated in caveolae [43]. This protein interacts with a large C-terminal domain of cPLA 2 , inhibiting its enzymatic activity [44]. Also, phosphatidylinositol 4,5-bisphosphate, which is concentrated in caveolae [45], interacts with a putative pleckstrin homology domain of cPLA 2 , resulting in increased enzymatic activity [17].…”

Redox regulation of annexin 2 and its implications for oxidative stress-induced renal carcinogenesis and metastasis

“…The second major function of Anx2 is acting as a phopholipase A 2 inhibitor in combination with p11 (Haigler et al, 1987;Wu et al, 1997) involved in the inhibition of platelet aggregation, which is in accord with the recent finding that Anx2 itself is a cell-surface receptor for plasminogen and its activator t-PA (tissuetype plasminogen activator) (Hajjar and Menell, 1997). Furthermore, abnormally high levels of Anx2 on acute promyelocytic leukemia cells were found to increase the production of plasmin, a fibrinolytic protein, suggesting that overexpression of Anx2 may be responsible for the hemorrhagic complications of acute promyelocytic leukemia (Menell et al, 1999).…”

Cytosolic phospholipase A2: physiological function and role in disease

“…Activation of cPLA 2 ␣ in vascular smooth muscle cells by calcium/calmodulin-dependent kinase II that phosphorylates S515 has been described ( 101 ). Phosphorylation of cPLA 2 ␣ on S727 by MAPK-interacting kinase does not enhance catalytic activity per se, but blocks its binding to an inhibitory complex in the cytosol composed of p11(S100A10)/annexin A2 ( 74,(102)(103)(104)(105) ( Fig. 1 ).…”