PD-1 /PD-L1 Adoptive Checkpoint Biosynthesis Separately Are Regulated By Gamma Common Which Regulate PD-1, Globin, and IFN-Gamma

Abstract

PD-1 /PD-L1 is adoptive checkpoint mechanism, where PD-1 is an adopting its PD-L1 ligand activities by presence of specific helical kinase proteins in its compositions: _gamma common chains,_LNK” lymphocyte adaptor protein, _or SH2B adaptor _protein “tyrosine kinases, and _”SOCS” suppressor of cytokine signaling, that specified for controlling PD-1 and PD-L1 bindings activity through temporary resting the PD-L1 and consequently T-cells activities then transform incoming signals to exogenous processes in favor the of proper immune functions, But the permanent inhibition of PD-1 /PD-L1 binding is due to breaking down or inhibition in one or more of the adaptors helical proteins (lymphocyte adaptor protein, or SH2B) with the presence of SOCS” suppressor of cytokine signaling that will increase stability of binding without adopting and without activities, but cells survival can still exist through presence of tyrosine kinases , interferon stimulate kinases ,and gamma common.

Where, deficiency in lymphocyte adaptor protein, or SH2B adaptors with presence of “SOCS” suppressor of cytokine signaling in PD-1 will stimulate and increase binding stability of PD-1 to PD-L1 ligand (that. Can described as idle status of binding of PD-1 to PD-L1), that can lead to inhibition in T-cells activities. Cells death can started by broken antigens, ribosomal substances, OPA1 membrane and PD-L1 that will lead to releasing PD-1 due to its origin is related to Ser /Thr phosphorylation pathways. PD-1 biosynthesis is regulated by proper active Gamma-chain productions which produced and activated by JAK stat signals pathways which has the function of stimulating OPA1 synthetase oxidative functions in availability of NF-κB (that activate proper transcription, and binding via several intermediate steps, leads to an interaction with IκB kinase ) for activating IFN-gamma productions that will regulate and stabilize PD-1 , PD-L1, MHC-class-I, MHC class II, then SIRPα1 for TLR4 proliferation activities respectively.

ITSM is a conserved sequence of amino acids concluded in PD-1 cytoplasmic tail that found intracellularly in cytoplasm, but ITSM receptors can be found as gamma (on the surface of cells in PD-1), beta (in PD-1 within cells or on surface of cells) , or alpha (that its receptors found in PD-L1) and is carrying out the functions and responsibility of promoting and adopting their cellular activities including anti-inflammatory processes , that can transform transmitted signals to exogenous processes through the interactions of SHP-1 and SHP-2 that the absence “LNK” lymphocyte adaptor protein or SH2B adaptor protein From PD-1 will lead to missing the Adoptive functions in PD-1 that lead to continually binding of PD1 to PD-L1 that inhibit T-cells).

Absence or dysfunction of PD-1 activities (which has Antitumor and anti inflammation activities) can be due to the Incorrectly composition from helical proteins which build PD-1 that will be the result of promoting accumulations of more cytotoxic and increase inflammation, and survival of cancer invasion .

Gamma common and some other helical proteins such as: LNK lymphocyte adaptor protein, or SH2B adaptor protein 3, tyrosine kinases, and SOCS suppressor of cytokine signaling are regulating both globin and PD-1 biosynthesis, that both PD-1 and hemoglobin are having the function of recovering each other’s in proper conditions in vivo (in presence of proper NFκB & OPA1 enzymes), Where, in the proper biological condition the activations of NF-κB and OPA1 activities will expand cells survival.