What is Type of Cytokine Receptor Family?
A central feature of type III protein secretion machines is their ability to engage their substrates in a hierarchical and organized fashion. The hierarchy in the secretion process is first observed during the assembly of the type III secretion injectisome when the secretion machine exclusively engages proteins required for building the needle complex substructure (early substrates). After completion of the needle complex, the secretion system loads the proteins that will form the needle tip substructure as well as the protein translocases (middle substrates), which upon contact with host cells will mediate the passage of effectors (late substrates) through the host plasma membrane. The hierarchy of the secretion process is orchestrated by a very large cytoplasmic complex known as the sorting platform, which selects and initiates the substrates into the secretion pathway.
Type III collagen binding protein (TIIICBP) was previously described as a platelet membrane protein that recognizes the KOGEOGPK peptide sequence within type III collagen. There are high biochemical and functional similarities between TIIICBP and kindlin-3, a member of a family of focal adhesion proteins. Similarly to anti-TIIICBP antibodies and the KOGEOGPK peptide, anti-kindlin-3 antibodies inhibited platelet interactions with type III collagen under flow conditions and slowed down platelet aggregation induced by glycoprotein VI agonists; e.g. collagen-related peptides and convulxin. In addition, the anti-kindlin-3 antibody inhibited platelet aggregation induced by low - but not high - doses of ADP or thrombin which depends on α(IIb)β(3) integrin function. the peptides identified by mass spectrometry from purified TIIICBP correspond to the kindlin-3 protein and demonstrate biochemical and functional similarities between TIIICBP and kindlin-3, strengthening a key role for TIIICBP/kindlin-3 in platelet interactions with collagen by cooperating with glycoprotein VI activation and integrin clustering in focal adhesion complexes.
Type III protein S deficiency is characterized by a low plasma level of free protein S, whereas the total concentration of protein S is normal. In contrast, both free and total protein S levels are low in type I deficiency. type I and type III deficiencies are phenotypic variants of the same genetic disease and that the low plasma concentrations of free protein S in both types are the result of an equimolar relationship between protein S and C4BP beta+.
Understanding the mechanism of action of Type of Cytokine Receptor Family has the potential to identify new drug targets for the treatment of certain diseases.