TAILIEUCHUNG - Báo cáo khoa học: Activation of p21-activated kinase 1 is required for lysophosphatidic acid-induced focal adhesion kinase phosphorylation and cell motility in human melanoma A2058 cells

Lysophosphatidicacid (LPA), oneof thenaturallyoccurring phospholipids, stimulates cellmotility through theactivation of Rho family members, but the signaling mechanisms remain tobe elucidated. In thepresent study,we investigated the roles of p21-activated kinase 1 (PAK1) onLPA-induced focal adhesion kinase (FAK) phosphorylation and cell motility. Treatment of human melanoma cells A2058 with LPA increased phosphorylation and activation of PAK1, which was blocked by treatment with pertussis toxin and by inhibition of phosphoinositide 3-kinase (PI3K) with an inhibitor LY294002 or by overexpression of catalytically inactive mutant of PI3Kc, indicating that LPA-induced PAK1 activation was mediated via a Gi protein and the PI3Kcsignalingpathway | Eur. J. Biochem. 271 1557-1565 2004 FEBS 2004 doi Activation of p21-activated kinase 1 is required for lysophosphatidic acid-induced focal adhesion kinase phosphorylation and cell motility in human melanoma A2058 cells In Duk Juna1. Janasoon Lee1. Kvuna Bok Lee1. Chana Gvo Park1 Yona Kee Kim2. Dona Wan Seo3 Donaeun Park4 Hyana Woo Lee5 Jeuna-Whan Han5 and Hoi Youna Lee1 1College of Medicine Konyang University Nonsan Korea 2College of Medicine Kwandong University Gangneung Korea 3Laboratory of Pathology NCI National Institutes of Health Bethesda MD USA 4School of Biological Sciences Seoul National University Korea 5College of Pharmacy Sungkyunkwan University Suwon Korea Lysophosphatidic acid LPA one of the naturally occurring phospholipids stimulates cell motility through the activation of Rho family members but the signaling mechanisms remain to be elucidated. In the present study we investigated the roles of p21-activated kinase 1 PAK1 on LPA-induced focal adhesion kinase FAK phosphorylation and cell motility. Treatment of human melanoma cells A2058 with LPA increased phosphorylation and activation of PAK1 which was blocked by treatment with pertussis toxin and by inhibition of phosphoinositide 3-kinase PI3K with an inhibitor LY294002 or by overexpression of catalytically inactive mutant of PI3Ky indicating that LPA-induced PAK1 activation was mediated via a Gi protein and the PI3Ky signaling pathway. In addition we demonstrated that Rac1 Cdc42 signals acted as upstream effector molecules of LPA-induced PAK activation. However Rho-associated kinase MAP kinase kinase 1 2 or phospholipase C might not be involved in LPA-induced PAK1 activation or cell motility stimulation. Furthermore PAK1 was necessary for FAK phosphorylation by LPA which might cause cell migration as transfection of the kinase deficient mutant of PAK1 or PAK auto-inhibitory domain significantly abrogated LPA-induced FAK phosphorylation. Taken together these findings

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