title: Focal Adhesion Kinase Directly Interacts with TSC2 Through Its FAT Domain and Regulates Cell Proliferation in Cashmere Goat Fetal Fibroblasts.
abstract: Focal adhesion kinase (FAK) is a cytoplasmic nonreceptor tyrosine kinase that senses a variety of extracellular signals, such as growth factors and integrins, to control the process of cell proliferation and metabolism. We cloned three goat FAK transcript variants (KM655805, KM658268, and KM658269) that encode 1052, 1006, and 962 amino-acid residue proteins. Bioinformatics analysis indicated that the putative FAK protein contains an FERM domain, a PTK domain, two Proline-rich regions, and a focal adhesion-targeting (FAT) domain. All the three transcript variants of FAK were detected in seven different goat tissues, and variant 1 had the most accumulation whereas variant 2 and variant 3 had lower accumulation. Treatment of goat fetal fibroblasts (GFbs) with a specific FAK inhibitor, TAE226, inhibited cell proliferation (p < 0.05) and induced damage to the cell morphology in a dose- and time-dependent manner. Further research demonstrated that FAK directly interacted with TSC2 (Tuberous sclerosis 2) tuberin domain through its C-terminus, which contains the complete FAT domain. In conclusion, our results indicated that FAK may be widely expressed in Cashmere goat tissues and its products participate in the mammalian target of rapamycin signaling pathway and cell proliferation through a direct interaction with TSC2 in GFBs.
authors.affiliation: 1 College of Life Sciences, Inner Mongolia University , Hohhot, People's Republic of China .|2 Hulunbeier Municipal People's Hospital , Hailaer, People's Republic of China .
authors.forename: Xu
authors.initials: X
authors.lastname: Zheng
authors.affiliation: 1 College of Life Sciences, Inner Mongolia University , Hohhot, People's Republic of China .
authors.forename: Wenlei
authors.initials: W
authors.lastname: Bao
authors.affiliation: 1 College of Life Sciences, Inner Mongolia University , Hohhot, People's Republic of China .
authors.forename: Jiaofu
authors.initials: J
authors.lastname: Yang
authors.affiliation: 1 College of Life Sciences, Inner Mongolia University , Hohhot, People's Republic of China .
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: 3 Department of Oncology, Kailuan General Hospital , Tangshan, People's Republic of China .
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Sun
authors.affiliation: 1 College of Life Sciences, Inner Mongolia University , Hohhot, People's Republic of China .
authors.forename: Yan
authors.initials: Y
authors.lastname: Liang
authors.affiliation: 1 College of Life Sciences, Inner Mongolia University , Hohhot, People's Republic of China .
authors.forename: Shuyu
authors.initials: S
authors.lastname: Li
authors.affiliation: 1 College of Life Sciences, Inner Mongolia University , Hohhot, People's Republic of China .
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 1 College of Life Sciences, Inner Mongolia University , Hohhot, People's Republic of China .
authors.forename: Xue
authors.initials: X
authors.lastname: Feng
authors.affiliation: 1 College of Life Sciences, Inner Mongolia University , Hohhot, People's Republic of China .
authors.forename: Huifang
authors.initials: H
authors.lastname: Hao
authors.affiliation: 1 College of Life Sciences, Inner Mongolia University , Hohhot, People's Republic of China .
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D049109:Cell Proliferation / Q000187:drug effects; D003001:Cloning, Molecular; D005333:Fetus; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006041:Goats; D008297:Male; D008958:Models, Molecular; D009025:Morpholines / Q000494:pharmacology; D061251:Primary Cell Culture; D011485:Protein Binding; D000072417:Protein Domains; D017433:Protein Structure, Secondary; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D009025:Morpholines; D012333:RNA, Messenger; C524632:TAE226; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D051416:Focal Adhesion Protein-Tyrosine Kinases