A Mini-Review Towards the Assessment of two Natural Anticoagulants Protein C And Antithrombin III |Biomedgrid

During the past decades several new anticoagulative proteins have been identified that play an important role in the regulation of hemostatic balance [1]. These proteins included antithrombin III(ATIII), protein C and its inhibitor, protein S, and thrombomodulin. In except for ATIII, the others form the components of the protein C pathway. The cDNA codes for human protein C protein which consists of a preproleader sequene of 42 amino acids, a light chain region of 155 amino acids, a connecting dipeptide of lys-Arg, and a heavy chain region of 262 amino acids [2,3]. During intracellular processing, the prepare leader sequence is removed, protein C is secreted as a mature protein of 419 amino acids. Protein C (PC), a vitamin K-dependent plasma protein, and its inhibitor of activated protein C (APCI) are part of a major regulatory system of hemostasis. Activated protein C destroys the activity of activated factor V and VIII. Protein S as cofactor of activated protein C (APC) is due to the inability of APC to prolong the APTT or the Va-induced clotting time in protein S deficient plasma [4]. APC and protein S complex could inactivate factor Va and VIIIa more rapidly under the condition of calcium and phospholipids than did APC alone [5,6]. More recent, it has been found that protein S drives cancer cell proliferation and cell survival via oncogenic receptor Axl [7-12]. Aberrant activation of RTKs often leads to malignant transformation, whereas PI3K/ Axl is required for this oncogenic receptor signaling [13]. Targeting against a deregulated dominant oncogenic receptor such as the oncogenic estrogen receptor (ER) pathway (tamoxifen), and blocking oncogenic receptor HER3/HER2 agent trastuzumab is enough to slow tumor progression [14-32].