Dock11 also known as Zizimin2, is a large (~240 kDa) protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 involved in intracellular

Intracellular

Not to be confused with intercellular, meaning "between cells".In cell biology, molecular biology and related fields, the word intracellular means "inside the cell".It is used in contrast to extracellular...

 signalling networks. It is a member of the DOCK-D subfamily of the DOCK

DOCK (protein)

DOCK is a family of related proteins involved in intracellular signalling networks. Studies to date suggest that this family act as guanine nucleotide exchange factors for small G proteins of the Rho family, such as Rac and Cdc42...

 family of guanine nucleotide exchange factor

Guanine nucleotide exchange factor

Guanine nucleotide exchange factors activate monomeric GTPases by stimulating the release of guanosine diphosphate to allow binding of guanosine triphosphate . A variety of unrelated structural domains have been shown to exhibit guanine nucleotide exchange activity...

s (GEFs) which function as activators of small G protein

G protein

G proteins are a family of proteins involved in transmitting chemical signals outside the cell, and causing changes inside the cell. They communicate signals from many hormones, neurotransmitters, and other signaling factors. G protein-coupled receptors are transmembrane receptors...

s. Dock11 activates the small G protein Cdc42

CDC42

Cell division control protein 42 homolog also known as CDC42 is a protein involved in regulation of the cell cycle. In humans, CDC42 is encoded by the CDC42 gene.- Function :...

.

Discovery

Dock11 was identified as a protein which is highly expressed

Gene expression

Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...

 in Germinal center

Germinal center

Germinal centers are sites within lymph nodes where mature B lymphocytes rapidly proliferate, differentiate, mutate their antibodies , and class switch their antibodies during a normal immune response to an infection...

 B lymphocytes. Subsequent RT-PCR analysis revealed expression of this protein in the spleen

Spleen

The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...

, thymus

Thymus

The thymus is a specialized organ of the immune system. The thymus produces and "educates" T-lymphocytes , which are critical cells of the adaptive immune system....

, bone marrow

Bone marrow

Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...

 and in peripheral blood lymphocytes

Peripheral Blood Lymphocytes

Peripheral blood lymphocytes are mature lymphocytes that circulate in the blood, rather than localising to organs . They comprise T cells, NK cells and B cells....

. Dock11 is expressed at lower levels in NIH-3T3 fibroblasts

3T3 cells

3T3 cells come from a cell line established in 1962 by two scientists then at the Department of Pathology in the New York University School of Medicine, George Todaro and Howard Green. The 3T3 cell line has become the standard fibroblast cell line...

, C2C12 myoblast

Myoblast

A myoblast is a type of embryonic progenitor cell that gives rise to muscle cells .The muscle cells can be skeletal muscle, smooth muscle, and cardiac muscle....

s and Neuro-2A neuroblastoma

Neuroblastoma

Neuroblastoma is the most common extracranial solid cancer in childhood and the most common cancer in infancy, with an annual incidence of about 650 cases per year in the US , and 100 cases per year in the UK . Close to 50 percent of neuroblastoma cases occur in children younger than two years old...

 cells. Dock11 mRNA has also been detected in the pars intermedia

Pars intermedia

Pars intermedia is the boundary between the anterior and posterior lobes of the pituitary. It contains three types of cells - basophils, chromophobes, and colloid-filled cysts. The cysts are the remainder of Rathke’s pouch....

.

Structure and Function

Dock11 exhibits the same domain

Protein domain

A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...

 arrangement as other memebrs of the DOCK-D/Zizimin subfamily and shares the highest level of sequence identity with Dock9

DOCK9

Dock9 , also known as Zizimin1, is a large protein involved in intracellular signalling networks. It is a member of the DOCK-D subfamily of the DOCK family of guanine nucleotide exchange factors which function as activators of small G proteins...

. It contains a DHR2 domain

DHR2 domain

DHR2 , also known as CZH2 or Docker2, is a protein domain of approximately 450-550 amino acids that is present in the DOCK family of proteins. This domain functions as a guanine nucleotide exchange factor domain for small G proteins of the Rho family...

 which mediates GEF activity and a DHR1 domain

DHR1 domain

DHR1 , also known as CZH1 or Docker1, is a protein domain of approximately 200-250 amino acids that is present in the DOCK family of signalling proteins. This domain binds phospholipids and so may assist in recruitment to cellular membranes. There is evidence that this domain may also mediate...

 domain which may interact with membrane

Cell membrane

The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...

 phospholipid

Phospholipid

Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...

s. It also contains an N-terminal PH domain which may be involved in its recruitment to the plasma membrane. Dock11 binds and activates nucleotide

Nucleotide

Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...

-free Cdc42 via its DHR2 domain and has also been reported to mediate positive feedback

Positive feedback

Positive feedback is a process in which the effects of a small disturbance on a system include an increase in the magnitude of the perturbation. That is, A produces more of B which in turn produces more of A. In contrast, a system that responds to a perturbation in a way that reduces its effect is...

 on active, GTP

Guanosine triphosphate

Guanosine-5'-triphosphate is a purine nucleoside triphosphate. It can act as a substrate for the synthesis of RNA during the transcription process...

-bound Cdc42, although this interaction required a small N-terminal region of Dock11 in addition to the DHR2 domain. Cdc42 in turn regulates signaling pathways that control diverse cellular functions including morphology

Morphology (biology)

In biology, morphology is a branch of bioscience dealing with the study of the form and structure of organisms and their specific structural features....

, migration

Cell migration

Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular directions to specific locations...

, endocytosis

Endocytosis

Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...

 and cell cycle

Cell cycle

The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...

 progression. Gene expression studies have suggested that Dock11 may have a role in the development of pituitary and testicular

Testicular cancer

Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system.In the United States, between 7,500 and 8,000 diagnoses of testicular cancer are made each year. In the UK, approximately 2,000 men are diagnosed each year. Over his lifetime, a man's risk of...

tumours.

Further reading