Receptor tyrosine kinases (RTK), polypeptide growth factors, many are high affinity receptors on the cell surface hormone and cytokine. Tyrosine kinase gene 90 unique identification codes for 58 protein, a receptor tyrosine kinase in the human genome. The receptor tyrosine kinases, it is not only an important regulator of normal cellular processes, it does not have an important role in the development and progression of many cancers is shown. Receptor tyrosine kinases are part of a large family of protein tyrosine kinases, receptor tyrosine kinases, comprising a protein containing the non-receptor tyrosine kinase and the transmembrane domain, do not have a transmembrane domain.
RTK Most, a receptor subunit single, but exist as multimeric complexes, for example, dimers disulfide-linked in the absence of hormone, insulin receptor or more of the ligand-binding extracellular domain is, I will induce the formation of dimer receptor. Has a hydrophobic transmembrane domain, each monomer is composed of the intracellular C-terminal region amino acids 25-38 pieces, and the extracellular N-terminal region, is coated. Extracellular N-terminal region, cysteine-rich characteristic to each sub-family of RTK epidermal growth factor (EGF)-like domain, or a fibronectin type III repeats, or shows the elements that are stored various comprising immunoglobulin (Ig) mainly, the domain that binds to the extracellular ligand such as hormone.The intracellular C-terminal region that shows the highest level of protection or certain growth factors, such as this, they include the ligand binding site, such as area,, contains the catalytic domain responsible for the kinase activity of these receptors, which catalyzes the tyrosine phosphorylation of the substrate and RTK receptor.
Through various means, usually, receptor dimerization occurs or the extracellular ligand binding is stable. This is because the cytoplasmic tyrosine receptor portion of each monomer, can be can be trans-phosphorylated by the partner receptor propagates a signal across the plasma membrane. Phosphorylation of specific tyrosine residues of the activated receptor, which creates a binding site and binding phosphotyrosine (SH2) domain (PTB) domain-containing protein Src homology 2. A particular protein domain of these is included, contains the phospholipase Cγ and Src. Phosphorylation and activation of these two proteins of the receptor binding results in the initiation of signal transduction pathways. Interact with the action of the activated receptor as an adapter protein, and other proteins that are not inside the enzymatic activity of their own.
This connection adapter proteins, activation of the RTK signaling pathway downstream such as MAP kinase signaling cascades such. Examples of signal transduction pathways associated, c-Met of the tyrosine kinase receptor is required for the survival and growth of the osteoblast migration of myogenic time and the like. Lack of the c-MET of prevents LBX1-the formation of limb muscles to distort the muscle formation secondary. The local action of the FGF and its receptor RTK classification paracrine signaling.
The tyrosine kinase, different processes, functions and behavior pathway, is responsible for the important events in the body. Whereas cell function in tyrosine kinase in the signal transduction to the nucleus, and receptor tyrosine kinase function in transmembrane signaling. Tyrosine kinase activity of the nucleus, like cell cycle control, the nature of the transcription factor. Thus, in practice, the tyrosine kinase activity are involved in mitogenesis, the induction of mitosis in cells of proteins and cytoplasmic proteins in the nucleus, the phosphorylated tyrosine residues in this process are. Growth and proliferation of cells can be dependent on the tyrosine kinase to some extent. The not including the chromatin, tyrosine kinase function is observed in the nuclear matrix to “fiber network” help to stabilize the native DNA or nuclear membrane.
Specifically, type family kinases, appears to control the cell cycle in the src that is defined phosphorus, in the nuclear matrix. Src family tyrosine kinases are closely related, but I shows the wide variety of functions. During cell growth and differentiation, as well as expression of tyrosine kinase Src family or roll will vary depending on the cell type considerably. Can function in signal transduction pathways are known Src tyrosine kinase phosphorylation and as a whole. Phosphorus, there is evidence that they are located in the cell membrane. Phosphorus is coupled receptor molecules functionally different and physically. And a higher activity of tyrosine in the cell matrix which has been converted from polyoma virus – type cell synthesizing collagen and extracellular matrix involved in wound healing – fibroblasts. Also, the tyrosine kinase activity, phosphorylation of the central T antigen tyrosine correlation determines that it is associated with the change is the same cell transformation, and regeneration or cell proliferation is also demonstrated in cells transformation.It are.
The transmission of regulatory signals and mechanical forces, it is very basic to the normal survival of the organism. Protein tyrosine kinases also play a role in this problem. As can be seen by immunofluorescence localization of the kinase, a protein tyrosine kinase, so called pp125 to hand the effects of focal adhesion of cells. Focus adhesion is a polymer structure that functions in the transmission of regulatory signals and mechanical forces. Among scholars, pp125 is also known as thanks to the presence of FAK (focal adhesion kinase), in cell adhesion plaques described above. Protein tyrosine kinase pp125 is one of the major phosphorylated tyrosine-containing proteins (fibroblasts, has been described in some detail above) of fibroblasts rodent and bird in the (non-transformed) intact cells some. Among the important work but a relatively small number of other frequently or occasionally take place, fibroblasts are responsible for cell type of cell structure and wound healing in animals.
Structure and sequence of pp125 is able to sense that there may be a new member of the protein tyrosine kinase family that, a very unique compared to the database of GenBank and National Biomedical Research Foundation. The protein tyrosine kinase is up to about 70% of the unique as compared to numbers in contrast to those protein tyrosine kinases other, between members of the protein tyrosine kinase known. Further, dubbing implicitly, the amino acid sequence is meant to be associated in the cytoplasm, which is one of the major groups of cytoplasmic protein tyrosine kinases. Monoclonal antibodies were found when knowing it was observed. chicken embryo cells of a monoclonal antibody that has been converted by pp60v-SRC recognizes the protein-containing phosphorus seven different. One of these monoclonal antibodies called 2A7, is pp125, in fact, supports the idea that a protein tyrosine kinase, to recognize pp125.
Cell growth is described in detail as described above, may be called a part of tyrosine kinases. Tyrosine kinase function is observed in the nuclear matrix. Member of the Src family of tyrosine kinases, of can be included kinase of a type that is the first to be described phosphorus, the nuclear matrix, the core of the calcium-induced differentiation kertinocytes. Phosphorus, got a job with the DNA matrix to the nuclear matrix in the “web” fiber stability and nuclear membrane physically. Further, the condition that the cell cycle were found. The contribution of tyrosine kinase protein phosphorus general nuclear matrix which is extracted to be able to control an accurate measurement only partially its activity, however, Lin is known. Phosphorus polypeptides are associated with tyrosine kinase activity of the nuclear matrix. Provides support for this idea, lesson phosphate is enzymatically active.