Pleckstrin-2 selectively interacts with phosphatidylinositol 3-kinase lipid products and regulates actin organization and cell spreading.
Pleckstrin-2 (PLEK2) has been implicated to be regulated by phosphatidylinositol (PI) 3-kinase, while pleckstrin1 (PLEK1) has been suggested to be a major PKC substrate in platelets. In this paper, we confirmed that PLEK2 specifically bound to the PI 3-kinase products in vitro and explored its behavior. PLEK2 was found to be expressed in various adherent cell lines, while PLEK1 expression was restricted to non-adherent cells in the protein level. Expression of PLEK2 in COS1 cells induced formation of protrusive F-actin structure and enhanced the actin rearrangements induced on collagen- or fibronectin-coated plates. A PLEK2 mutant incapable of binding to the PI 3-kinase products did not show any effect on actin rearrangement. Knockdown of PLEK2 by shRNA inhibited spreading of HCC2998 adenocarcinoma cells. PLEK2 colocalized with Rac and was suggested to be oligomerized. These results suggest that PLEK2 is involved in actin rearrangement in a PI 3-kinase dependent manner.
Department of Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Norihisa
N
Hamaguchi
Sayoko
S
Ihara
Tsutomu
T
Ohdaira
Hiromichi
H
Nagano
Akihiro
A
Iwamatsu
Hiroyuki
H
Tachikawa
Yasuhisa
Y
Fukui
D000199:Actins / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D048430:Cell Shape; D002522:Chlorocebus aethiops; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D020744:rac GTP-Binding Proteins / Q000378:metabolism
D000199:Actins; D008565:Membrane Proteins; D019869:Phosphatidylinositol 3-Kinases; D018129:Phosphatidylinositol Phosphates; D020744:rac GTP-Binding Proteins; C120651:PLEK2 protein, human; C060974:phosphatidylinositol 3,4,5-triphosphate