Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility. Functions as a guanine nucleotide exchange factor (GEF), which activates Rac Rho small GTPases by exchanging bound GDP for free GTP. Its GEF activity may be enhanced by ELMO1.
Tissue specificity: Highly expressed in placenta, lung, kidney, pancreas and ovary. Expressed at intermediate level in thymus, testes and colon.
Function:
Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility. Functions as a guanine nucleotide exchange factor (GEF), which activates Rac Rho small GTPases by exchanging bound GDP for free GTP. Its GEF activity may be enhanced by ELMO1.
Subunit:
Interacts with the SH3 domains of CRK and NCK2 via multiple sites. Interacts with nucleotide-free RAC1 via its DHR-2 domain. Interacts with ELMO1, ELMO2 and probably ELMO3 via its SH3 domain. Interacts with RAC1 and BAI1.
Subcellular Location:
Cytoplasm (Probable). Membrane (Probable). Note=Recruited to membranes via its interaction with phosphatidylinositol 3,4,5-trisphosphate (Probable).
Tissue Specificity:
Highly expressed in placenta, lung, kidney, pancreas and ovary. Expressed at intermediate level in thymus, testes and colon.
Similarity:
Belongs to the DOCK family.
Contains 1 DHR-1 domain.
Contains 1 DHR-2 domain.
Contains 1 SH3 domain.
SWISS:
Q14185
Gene ID:
1793
Database links:
Entrez Gene: 1793 Human
Entrez Gene: 330662 Mouse
Entrez Gene: 309081 Rat
Omim: 601403 Human
SwissProt: Q14185 Human
SwissProt: Q8BUR4 Mouse
Unigene: 159195 Human
Unigene: 645702 Human
Unigene: 436572 Mouse
乳腺癌转移的新标记物DOCK1
乳腺癌是一种常常发生转移的癌症。将近90%的乳腺癌患者都因为癌症扩散而死，因此，理解这一危险过程的细胞和分子基础机制是十分重要的。
近日，加拿大蒙特利尔临床研究所（Institut de recherches cliniques de Montreal, IRCM）的科学家在乳腺癌研究方面取得了一个重要的发现，他们确定了，一种名为DOCK1的蛋白质可以作为潜在的靶标用于减少乳腺癌患者的癌转移。相关研究结果刊登在了近期出版的《PNAS》上。
研究人员在乳腺癌治疗方面尽管已经取得了重要的进展，但是对于癌症扩散的机制却知之甚少。科学家正在试图确定能够调节癌转移过程的蛋白质，因为它们或许可以作为新的药物靶标，并与现有的方法相结合促进治疗的效果。
在这项研究中，2个主要的癌症亚型——HER-2+型和Basal-like型，很容易转移和复发，并最终导致患者的低生存率。该调查以HER-2+(人类表皮生长因子受体2)型为研究对象， 这代表了大约25%的乳腺癌病例。 HER2阳性肿瘤比其它类型的肿瘤更倾向于快速的发展和扩散。
研究人员解释到，通过研究HER2+乳腺癌小鼠模型，确定了DOCK1蛋白质是癌转移的一个重要的调控因子。当去除了小鼠中的这一蛋白质后，乳腺癌的肺转移大大减少了。此外，研究发现DOCK1蛋白质有助于肿瘤的生长。
为了证明DOCK1的表达与乳腺癌预后之间的关系，研究人员对包含患者基因信息的几个数据库进行了分析。结果发现，在HER-2+型或Basal-like型乳腺癌中，高水平的DOCK1与较差的预后以及疾病的复发有关。
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Paraformaldehyde-fixed, paraffin embedded (Mouse testis); Antigen retrieval by boiling in sodium citrate buffer (pH6.0) for 15min; Block endogenous peroxidase by 3% hydrogen peroxide for 20 minutes; Blocking buffer (normal goat serum) at 37°C for 30min; Antibody incubation with (DOCK1) Polyclonal Antibody, Unconjugated (SL7110R) at 1:500 overnight at 4°C, followed by a conjugated secondary (sp-0023) for 20 minutes and DAB staining.
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