title: Formation of Kv2.1-FAK complex as a mechanism of FAK activation, cell polarization and enhanced motility.
abstract: Focal adhesion kinase (FAK) plays key roles in cell adhesion and migration. We now report that the delayed rectifier Kv2.1 potassium channel, through its LD-like motif in N-terminus, may interact with FAK and enhance phosphorylation of FAK(397) and FAK(576/577). Overlapping distribution of Kv2.1 and FAK was observed on soma and proximal dendrites of cortical neurons. FAK expression promotes a polarized membrane distribution of the Kv2.1 channel. In Kv2.1-transfected CHO cells, formation of the Kv2.1-FAK complex was stimulated by fibronectin/integrin and inhibited by the K(+) channel blocker tetraethylammonium (TEA). FAK phosphorylation was minimized by shRNA knockdown of the Kv2.1 channel, point mutations of the N-terminus, and TEA, respectively. Cell migration morphology was altered by Kv2.1 knockdown or TEA, hindering cell migration activity. In wound healing tests in vitro and a traumatic injury animal model, Kv2.1 expression and co-localization of Kv2.1 and FAK significantly enhanced directional cell migration and wound closure. It is suggested that the Kv2.1 channel may function as a promoting signal for FAK activation and cell motility.
authors.affiliation: Key Laboratory of Combined Multi-organ Transplantation of Ministry of Health China, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Wei
authors.forename: Ling
authors.initials: L
authors.lastname: Wei
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.forename: Zhong-Yang
authors.initials: ZY
authors.lastname: Lu
authors.forename: Kevin
authors.initials: K
authors.lastname: Francis
authors.forename: Xin-Yang
authors.initials: XY
authors.lastname: Hu
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Xiong
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Naren L
authors.initials: NL
authors.lastname: Banik
authors.forename: Shu-Sen
authors.initials: SS
authors.lastname: Zheng
authors.forename: Shan Ping
authors.initials: SP
authors.lastname: Yu
mesh_terms: D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion; D002462:Cell Membrane / Q000201:enzymology; D002465:Cell Movement / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D048430:Cell Shape; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D003315:Cornea / Q000503:physiopathology; D065306:Corneal Injuries; D006224:Cricetinae; D003412:Cricetulus; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005353:Fibronectins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D051379:Mice; D046912:Multiprotein Complexes; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation; D017354:Point Mutation; D026902:Potassium Channel Blockers / Q000494:pharmacology; D025941:Protein Interaction Mapping; D011554:Pseudopodia / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D051669:Shab Potassium Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019789:Tetraethylammonium / Q000494:pharmacology; D014162:Transfection; D014945:Wound Healing
chemical_list: D005353:Fibronectins; D016023:Integrins; C496990:Kcnb1 protein, mouse; D046912:Multiprotein Complexes; D026902:Potassium Channel Blockers; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D051669:Shab Potassium Channels; D019789:Tetraethylammonium; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse