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| title | chunk | source | category | tags | date_saved | instance |
|---|---|---|---|---|---|---|
| Biochemical cascade | 4/9 | https://en.wikipedia.org/wiki/Biochemical_cascade | reference | science, encyclopedia | 2026-05-05T10:46:07.942614+00:00 | kb-cron |
=== Lymphocytes === The main goal of biochemical cascades in lymphocytes is the secretion of molecules that can suppress altered cells or eliminate pathogenic agents, through proliferation, differentiation and activation of these cells. Therefore, the antigenic receptors play a central role in signal transduction in lymphocytes, because when antigens interact with them lead to a cascade of signal events. These receptors, that recognize the antigen soluble (B cells) or linked to a molecule on Antigen Presenting Cells (T cells), do not have long cytoplasm tails, so they are anchored to signal proteins, which contain a long cytoplasmic tails with a motif that can be phosphorylated (ITAM – immunoreceptor tyrosine-based activation motif) and resulting in different signal pathways. The antigen receptor and signal protein form a stable complex, named BCR or TCR, in B or T cells, respectively. The family Src is essential for signal transduction in these cells, because it is responsible for phosphorylation of ITAMs. Therefore, Lyn and Lck, in lymphocytes B and T, respectively, phosphorylate immunoreceptor tyrosine-based activation motifs after the antigen recognition and the conformational change of the receptor, which leads to the binding of Syk/Zap-70 kinases to ITAM and its activation. Syk kinase is specific of lymphocytes B and Zap-70 is present in T cells. After activation of these enzymes, some adaptor proteins are phosphorylated, like BLNK (B cells) and LAT (T cells). These proteins after phosphorylation become activated and allow binding of others enzymes that continue the biochemical cascade. One example of a protein that binds to adaptor proteins and become activated is PLC that is very important in the lymphocyte signal pathways. PLC is responsible for PKC activation, via DAG and Ca2+, which leads to phosphorylation of CARMA1 molecule, and formation of CBM complex. This complex activates Iκκ kinase, which phosphorylates I-κB, and then allows the translocation of NF-κB to the nucleus and transcription of genes encoding cytokines, for example. Others transcriptional factors like NFAT and AP1 complex are also important for transcription of cytokines. The differentiation of B cells to plasma cells is also an example of a signal mechanism in lymphocytes, induced by a cytokine receptor. In this case, some interleukins bind to a specific receptor, which leads to activation of MAPK/ERK pathway. Consequently, the BLIMP1 protein is translated and inhibits PAX5, allowing immunoglobulin genes transcription and activation of XBP1 (important for the secretory apparatus formation and enhancing of protein synthesis). Also, the coreceptors (CD28/CD19) play an important role because they can improve the antigen/receptor binding and initiate parallel cascade events, like activation o PI3 Kinase. PIP3 then is responsible for activation of several proteins, like vav (leads to activation of JNK pathway, which consequently leads to activation of c-Jun) and btk (can also activate PLC).
=== Bones ===
==== Wnt signaling pathway ==== The Wnt signaling pathway can be divided in canonical and non-canonical. The canonical signaling involves binding of Wnt to Frizzled and LRP5 co-receptor, leading to GSK3 phosphorylation and inhibition of β-catenin degradation, resulting in its accumulation and translocation to the nucleus, where it acts as a transcription factor. The non-canonical Wnt signaling can be divided in planar cell polarity (PCP) pathway and Wnt/calcium pathway. It is characterized by binding of Wnt to Frizzled and activation of G proteins and to an increase of intracellular levels of calcium through mechanisms involving PKC 50. The Wnt signaling pathway plays a significant role in osteoblastogenesis and bone formation, inducing the differentiation of mesenquimal pluripotent cells in osteoblasts and inhibiting the RANKL/RANK pathway and osteoclastogenesis.
==== RANKL/RANK signaling pathway ==== RANKL is a member of the TNF superfamily of ligands. Through binding to the RANK receptor it activates various molecules, like NF-kappa B, MAPK, NFAT and PI3K52. The RANKL/RANK signaling pathway regulates osteoclastogenesis, as well as, the survival and activation of osteoclasts.
==== Adenosine signaling pathway ==== Adenosine is very relevant in bone metabolism, as it plays a role in formation and activation of both osteoclasts and osteoblasts. Adenosine acts by binding to purinergic receptors and influencing adenylyl cyclase activity and the formation of cAMP and PKA 54. Adenosine may have opposite effects on bone metabolism, because while certain purinergic receptors stimulate adenylyl cyclase activity, others have the opposite effect. Under certain circumstances adenosine stimulates bone destruction and in other situations it promotes bone formation, depending on the purinergic receptor that is being activated.