PTPIP51, a novel 14-3-3 binding protein, regulates cell morphology and motility via Raf-ERK pathway.
Cell migration plays a critical role during the development of most organisms and the process of malignant tumor metastasis. In the present study, we investigated the role of PTPIP51 (protein tyrosine phosphatase interacting protein 51) in cell motility. Overexpression of PTPIP51 induced cell elongation, increased cell migration, adhesion, and spreading, while downregulation of PTPIP51 had the opposite effects. We demonstrated here, that PTPIP51 could regulate ERK activity on Raf level, since MEK inhibitor and dominant-negative Raf-1 but not Ras could inhibit the ERK activation induced by PTPIP51. Further studies proved that PTPIP51 could interact with Raf-1 through 14-3-3, suggesting that PTPIP51 is a regulator of the Raf-MEK-ERK cascade through modulation of Raf-1 by 14-3-3. In addition, two redundant 14-3-3 binding domains in the PTPIP51 protein have been identified by deletion/mutation studies. We conclude that PTPIP51 regulates cell morphology and cell motility via interaction with Raf-1 through 14-3-3, and that PTPIP51 binds to 14-3-3 through two redundant binding domains.
Yu
Chuanfei
C
Laboratory of Medical Immunology, School of Basic Medical Science, Peking University Health Science Center, 38# Xueyuan Road, Beijing, 100191, PR China.
Han
Wenling
W
Shi
Taiping
T
Lv
Bingfeng
B
He
Qihua
Q
Zhang
Yanfei
Y
Li
Ting
T
Zhang
Yingmei
Y
Song
Quansheng
Q
Wang
Lu
L
Ma
Dalong
D
D048948:14-3-3 Proteins / Q000378:metabolism*; D000595:Amino Acid Sequence; D054443:Cell Migration Assays; D002465:Cell Movement; D048430:Cell Shape; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D048490:raf Kinases / Q000378:metabolism*
D048948:14-3-3 Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D048490:raf Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048369:MAP Kinase Kinase 1; D017027:Protein Tyrosine Phosphatases; C515449:RMDN3 protein, human