Authors: Ashraf Marzouk El Tantawi.
Proper S6K /BTK and PLCγ2 are main regulations for thromboxane-A synthesis, and necessary for B-cell maturations and T-cells modulations and functions.
The main factors that cause the Osteoarthritis "OA" and diabetes and linked between them are the deficiency of Ser amino acids and decreasing or down regulations of Ser phosphorylation signaling pathway which necessary for proper S6K productions, where normally the Ser phosphorylation signaling pathway is the basis of Ser /Thr phosphorylation signaling which normally necessary for proper Akt, S6K1 synthesis and necessary for RORs and IFNs synthesis and also necessary for running proper BTK and proper PLCγ2 productions, where S6K is main regulator for ATPase and for proper PLCγ1 and for PLCγ2 synthesis which necessary for bone growth and for increasing and modulating immune efficiency.
Osteoarthritis "OA" is characterized by a sharp expression in Gamma-Phospholipase C-1 "PLCγ1", with decreasing "or inhibition" in PLCγ2 "PLC beta" productions.
The increasing in PLCγ1 with Deficiency in Ser amino acids will lead to deficiency in Ser phosphorylation signaling (which is main basis for Ser/Thr phosphorylation signaling which has the main function of producing proper S6K), and decreasing in synthase activity will reflect down regulations in BTK pathways and lead to inhibition in PLCγ2 productions which will reflect diabetes (inhibition in Estrogen with the production of Androgen instead of estrogen) and can reflect early Osteoarthritis "OA" prognosis depend on the percentage of Deficiency or inhibition in basic amino acids and in basic necessary signaling pathways.
The proper S6K are so necessary for reactivating both PLCγ1&2, where phospholipase Cγ2 (PLCγ2) is activated from a variety of cell surface receptors such as SyK "S6K".
As, the B cells are promoted by the function and activities of both PLCγ1&2, as the deficiency in Ser amino acids will reflect decreasing in Ser phosphorylation pathways and then decreasing in Estrogen synthesis, with increasing in Androgen synthesis which lead to decreasing in PLCs isoforms production and lead to pathogenic diabetes problem. So T2DM is strongly connected with OA disease and both are having the same syndrome of causing their pathogenic problems, and any early step from any of those two or more similar diseases can lead to the other.
Pathogenic type 2 diabetes associated with progressive beta-cell impairment due to the mutations in the production of normal insulin which due to missing of Ser phosphorylation signaling during mTOR Ser/Thr phosphorylation pathways that reflect Inhibition in
The releasing of PS/T-Thymine -Kinase and PS/T-Cytosine -kinase chains (mTORC1) which are regulating hydrophobic amino acids synthesis which can be modified by synthetase enzymes for creating the first active gamma-subunits (upon synthetase effects) that will be modified by synthase effect for Beta-subunit synthesis then for alpha subunits upon phospholipase effects respectively.
The previous of the releasing of PS/T-Thymine -Kinase and PS/T-Cytosine -kinase chains (mTORC1) from specifically the phosphorylations of Ser pathway is so necessary steps and mechanism for normal S6K productions, necessary for IFN-Gamma and for PLCγ1 productions, and therefore necessary for normal PLCγ2 synthesis which is necessary for B-cell activities, for T-cells modulations, for modulating anti-inflammatory steps and procedures, for thromboxane-A synthesis, and for bone growth and modulation.
Inhibition in PS/T-Thymine -Kinase and PS/T-Cytosine -kinase chains (mTORC1) productions can be the main reason for inhibition the beta subunits productions that can be the reason of decreasing in the hyperpolarization and then electrical activity will lead to decreasing in the abolition of Ça+ which will lead to increasing in the dropping in blood pressure.
Deficiency in conversion of glutarate to glutamate and decreasing in proline biosynthesis can affect on cartilage synthesis and bone growth due to decreasing in the activities of mitochondrial OPA1 oxidations.
It's imp to note that
Tyrosine phosphatase
PTPs are important regulator of chondrogenic patterning and are critical regulators of tyrosine phosphorylation that it's activity depends on Tyr, Ser synthesis (hydrophobic acids) and on JAK state signaling activities.
And so, the proline-rich tyrosine kinases regulate proper PLCs isoforms which compete for binding site at the very C terminus of fibroblast growth factor for osteprogenitor embryonic development, and bone formations.
Synthetase is the main regulator for PLCγ1 activities followed by synthase effects for beta-subunits ("PLCγ2") productions which is able to "upregulate phospholipase abtivity" for alpha subunits (PLC-alpha) productions for reactivating fibroblast growth factor receptor (FGFR2) and for reactivating antigens and TLR4 productions.
Where, PLCγ1 competes for a binding site at the very C terminus of FGFR2 for embryonic development and bones growth, where, PLCs isoforms are involved in multiple stages in TLR4, interferon, and in anti-inflammatory steps.
And also, PLCγ1 recruit to CSF-1 is following imp stages for producing PLCγ2 which is necessary for activating anti-inflammatory where, IFN-γ activates PLC-γ2 via an upstream of tyrosine kinase.
The PLCγ1 and PLCγ2 (PLCs) are so imp in anti-inflammatory processes and can be considered as having the main roles of characterizing the activities of thromboxane and fibrin through re-modulating immune and T cells activities.
Inhibitions or reduction or mutations in S6K, in BTK and in the original main normal PLCγ2 productions will cause an inherent or inhibition in CXCL12 then followed by inherent or inhibition in CXCR4 then reflect inherent or inhibition in the regulation of B-cell growth, migrations, adhesions and functions.
Proline amino acids is necessary for reactivate OPA1 anabolic oxidations (started by synthetase, then synthase, then phospholipase for producing gamma "PLCγ1", then beta "PLCγ2", then alpha "PLC-a" subunits respectively) for cartilage synthesis which promote PLCγ2 synthesis necessary for bone growth including antigen and thromboxane-A synthesis.
Porpoise of Study
Understanding the main reasons for causing chronic lymphocytic leukemia "CLL" where, proper S6K /BTK and PLCγ2 are main regulations for thromboxane-A synthesis and necessary for B-cells maturation and T-cells modulations.
Also, it's important to Understand main factors that cause and link the Osteoarthritis "OA" with diabetes which are the deficiency in Ser amino acids and mutated S6K production lead to deficiency or inhibition in Ser phosphorylation signaling which normally is the basis of Ser /Thr phosphorylation signaling which necessarily for Akt, S6K1 synthesis and necessary for RORs and IFNs synthesis and also necessary for proper PLCγ2 productions, where S6K is main regulator for ATPase and for proper PLCγ2 synthesis, that I have to note that the shortage ratio of amino acids (or enzymes or steps) is the ratio that can define the degree and type of specific disease that can differ from others which can linked together with the same Syndromes of disease, and also the shortage ratio between the beta Cytokines productions and the ratio of sudden high inflammations productions "and the type of its inflammatory molecules" have to be calculated and considered related to the patients ages (whether child, youth or old ages) and the duration of the chronic disease, that some can be confused to differentiate between auto-immune disease and regular disease problems diagnosis.
That, there was a case of a child with 9-year-old who had a suspicion of loose of bone maturation and growth, and has a sudden infection in the right lung and a lack of breathing with pain. It was found that there was a pulmonary abscess in right lung, and there was a development with the appearance of an air bag or "inflammatory fluid bag" surrounding respiratory cells in right side. The occurrence of inflammations molecules and their growth was rapid enough faster than IFNs productions and faster than PLCγ2 productions due to the age of the child "Note some her regular treating doctors diagnosed her medical conditions as a type Autoimmune disease and she has weakened immunity due to sudden fast infection related to her young age".
High lights
_ increasing in PLCγ1 with Deficiency in Ser, in proper S6K, and decreasing in synthase activity with inhibition in PLCγ2 will reflect decreasing in anti-inflammatory processes, reflect starting or increasing in Osteoarthritis syndromes, and also reflects the appearance of diabetes syndrome.
_proper healthy PLCγ2 are so necessary for increasing re-medulate immune efficiencies, and for re-modulate antigen and T-cells refunctions, and also proper healthy PLCγ2 production are so imp for recovery from osteoporosis and from both Osteoarthritis and diabetes.
_inhibition in PLCγ2 Bio-Synthesis can reflect decreasing or inhibition in Thromboxane-A 1 percentages and its Molecular structure.
Where, CLL characterized by inhibition in BTK, inhibition in PLCγ2 synthesis, inhibition in main antigen synthesis, and inhibition in the proper normal Thromboxane-A synthesis which regulated mainly by PLCγ1 then IFNs production then regulated by PLCγ2 proper productions.
_Chronic lymphocytic leukemia (CLL) observed during treatment with B-cell receptor inhibitors pathway including inhibitor of Bruton’s tyrosine kinase-PLCγ2, where, CLL can be strongly linked to Osteoporosis "OA", and linked to both Osteoarthritis and diabetes too.
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