An Annexin 2 Phosphorylation Switch Mediates p11-dependent Translocation of Annexin 2 to the Cell Surface

Abstract

Annexin 2 is a profibrinolytic co-receptor for plasminogen and tissue plasminogen activator that stimulates activation of the major fibrinolysin, plasmin, at cell surfaces. In human subjects, overexpression of annexin 2 in acute promyelocytic leukemia leads to a bleeding diathesis reflective of excessive cell surface annexin 2-de- Investig. 113, 38 -48). Here, we show that endothelial cell annexin 2, a protein that lacks a typical signal peptide, translocates from the cytoplasm to the extracytoplasmic plasma membrane in response to brief temperature stress both in vitro and in vivo in the absence of cell death or cell lysis. This regulated response is independent of new protein or mRNA synthesis and does not require the classical endoplasmic reticulumGolgi pathway. Temperature stress-induced annexin 2 translocation is dependent on both expression of protein p11 (S100A10) and tyrosine phosphorylation of annexin 2 because annexin 2 release is completely eliminated on depletion of p11, inactivation of tyrosine kinase, or mutation of tyrosine 23. Translocation of annexin 2 to the cell surface dramatically increases tissue plasminogen activator-dependent plasminogen activation potential and may represent a novel stress-induced protein secretion pathway.

S100A6 binds to annexin 2 in pancreatic cancer cells and promotes pancreatic cancer cell motility

“…This was further supported by the finding that depletion of S100A6 in cultured pancreatic cancer cells was found to result in diminished numbers of cells expressing membranous annexin 2. A similar relationship between annexin 2 and S100A10 was reported by Deora et al (2004) who studied the translocation of annexin 2 from the cytoplasm to the cell surface of endothelial cells after the application of mild heat. The authors found that depletion of S100A10 from endothelial cells resulted in reduced surface expression of annexin 2, indicating that S100A10 expression was important for cell surface translocation of annexin 2.…”

2D-DIGE analysis of phospho-enriched fractions from dasatinib-treated melanoma cell lines

“…SRC kinase can directly phosphorylate ANXA2 on Y23 [26,27], which may negatively modulate ANXA2 function and inhibit the ability of ANXA2 to bind F-actin [27]. However, another study showed that phosphorylation of ANXA2 Y23 is essential for ANXA2 function and its association with the endosome [19].…”

“…The ANXA2-S100A10 complex has a channel modulating effect on the cell surface which can affect the membrane interactions of lipids [29]. SRC kinase has been shown to phosphorlyate both ANXA2 [26,27] and S100A10 [30].…”

Alterations in Expression of p11 and SERT in Mucosal Biopsy Specimens of Patients With Irritable Bowel Syndrome

“…Conversely, mice with overexpression of p11 had increased 5-HT 1B receptor function and acted as is they were treated with an antidepressant. p 11 also facilitates the translocation of annexin II to the cell surface and the functional expression of ion channels (NaV1.8, TASK-1, TRPV5/6) was shown earlier (12)(13)(14)(15).…”