Abstract
Pleckstrin-2 is a member of pleckstrin family with well-defined structural features that was first identified in 1999. Over the past 20 years, our understanding of PLEK2 biology has been limited to cell spreading. Recently, increasing evidences support that PLEK2 plays important roles in other cellular events beyond cell spreading, such as erythropoiesis, tumorigenesis and metastasis. It serves as a potential diagnostic and prognostic biomarker as well as an attractive target for the treatment of cancers. Herein, we summary the protein structure and molecular interactions of pleckstrin-2, with an emphasis on its regulatory roles in tumorigenesis.
Highlights
Pleckstrin was first initially described as a prominent substrate of protein kinase C (PKC) in hematopoietic cells
PLEK2 exhibits distinct roles in other cellular events the phospholipid binding of PLEK2, it plays a role in membrane through the individual molecular interactions and regulatory ruffles and cell spreading by cooperating with pleckstrin homology (PH) domains mechanisms (Table 2)
Expression of PLEK1 results in cell spreading and rearrangement of cytoskeleton characterized by morphologic change such as formation of peripheral membrane ruffles or dorsal projection, which is dependent upon the Rac activity and integrin binding (Ma and Abrams, 1999; Roll et al, 2000; Bach et al, 2007)
Summary
Pleckstrin was first initially described as a prominent substrate of protein kinase C (PKC) in hematopoietic cells. It has been suggested that DEP interacts intramolecularly with the N-terminal PH domain to mediate membrane anchoring of PLEK1 (Civera et al, 2005) Such interaction may occur between two PLEK molecules, which accounts for the formation of irregular polymers of PLEK2. Examining the crude 3D model built with the sequence for mouse PLEK2, two putative small molecule binding grooves appear to exist near K13 and R14 residues (N-PH domain) and at K256 residues (C-PH domain), respectively. These sites have been suggested to be response for the phospholipid binding domains (Bach et al, 2007; Jackson et al, 2007). Due to the highly similarity of protein structural features, it is not surprise that both of these two pleckstrin proteins regulate cell protrusions such as lamellipodia and filopodia, which are important for cellular shape change and spreading (Figure 2)
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