Identification of integrin alpha1 as an interacting protein of protein tyrosine phosphatase PRL-3.
PRL-3 is a newly identified protein tyrosine phosphatase associated with tumor metastasis. It is over-expressed in various cancers, such as colorectal cancer, gastric cancer, and ovarian cancer, and is correlated with the progression and survival of cancers. Although PRL-3 plays a causative role in promoting cancer cell invasion and metastasis, the molecular mechanism is unknown. To investigate PRL-3's roles in tumorigenesis and signal transduction pathway, we screened the human placenta brain cDNA library with the bait of PRL-3 in yeast two-hybrid system. Then we identified integrin alpha1 as a PRL-3-interacting protein for the first time, and verified this physical association with pull-down and co-immunoprecipitation assays. Furthermore, we found that PRL-3 could down-regulate the tyrosine-phosphorylation level of integrin beta1 and increased the phosphorylation level of Erk1/2. Our present discovery will provide new clues for elucidating the molecular mechanism of PRL-3 in promoting cancer invasion and metastasis.
Department of Biochemistry and Molecular Biology, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing 100036, PR China.
Lirong
L
Peng
Genglin
G
Jin
Li
L
Wang
Jianpin
J
Guo
Lin
L
Meng
Chengchao
C
Shou
D000595:Amino Acid Sequence; D002460:Cell Line; D015536:Down-Regulation; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D039423:Integrin alpha1 / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D039641:Integrin beta Chains / Q000737:chemistry / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*
D017874:Immediate-Early Proteins; D039423:Integrin alpha1; D039641:Integrin beta Chains; D009363:Neoplasm Proteins; D019000:Phosphotyrosine; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases