WAVE2 forms a complex with PKA and is involved in PKA enhancement of membrane protrusions.
PKA contributes to many physiological processes, including glucose homeostasis and cell migration. The substrate specificity of PKA is low compared with other kinases; thus, complex formation with A-kinase-anchoring proteins is important for the localization of PKA in specific subcellular regions and the phosphorylation of specific substrates. Here, we show that PKA forms a complex with WAVE2 (Wiskott-Aldrich syndrome protein family verprolin-homologous protein 2) in MDA-MB-231 breast cancer cells and mouse brain extracts. Two separate regions of WAVE2 are involved in WAVE2-PKA complex formation. This complex localizes to the leading edge of MDA-MB-231 cells. PKA activation results in enlargement of the membrane protrusion. WAVE2 depletion impairs PKA localization at membrane protrusions and the enlargement of membrane protrusion induced by PKA activation. Together, these results suggest that WAVE2 works as an A-kinase-anchoring protein that recruits PKA at membrane protrusions and plays a role in the enlargement of membrane protrusions induced by PKA activation.
Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo, Kyoto 606-8502, Japan.
Hiroshi
H
Yamashita
Kazumitsu
K
Ueda
Noriyuki
N
Kioka
D054758:A Kinase Anchor Proteins; D000818:Animals; D001921:Brain / Q000166:cytology; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D022081:Cell Surface Extensions / Q000201:enzymology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D051379:Mice; D011485:Protein Binding; D021381:Protein Transport; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism*
D054758:A Kinase Anchor Proteins; D051300:Wiskott-Aldrich Syndrome Protein Family; D017868:Cyclic AMP-Dependent Protein Kinases