PRKCQ
Protein kinase C theta (PKC-) is an enzyme that in humans is encoded by the PRKCQ gene. PKC-, a member of serine/threonine kinases, is mainly expressed in hematopoietic cells with high levels in platelets and T lymphocytes, where plays a role in signal transduction. Different subpopulations of T cells vary in their requirements of PKC-, therefore PKC- is considered as a potential target for inhibitors in the context of immunotherapy.

# Function
Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by the second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role. The protein encoded by this gene is one of the PKC family members. It is a calcium-independent and phospholipid-dependent protein kinase. This kinase is important for T-cell activation. It is required for the activation of the transcription factors NF-kappaB and AP-1, and may link the T cell receptor (TCR) signaling complex to the activation of the transcription factors. PKC- also play a role in the apoptosis of lymphoid cells where it negatively influence and delay the aggregation of spectrin in an early phase of apoptosis.

## The role of PKC- in T cells
PKC- has a role in the transduction of signals in T cells, the kinase influences their activation, survival and growth. PKC- is important in the signal pathway integrating signals from TCR and CD28 receptors. A junction between an APC (an antigen presenting cell) and a T cell through their TCR and MHC receptors forms an immunological synapse. The active PKC- is localized in immunological synapse of T cells between the cSMAC (central supramolecular activation cluster containing TCR) and pSMAC (peripheral supramolecular activation cluster containing LFA-1 and ICAM-1). In regulatory T cells, PKC- is depleted depleted from the region of immunological synapse, whereas in effector T cells, PKC  is present. As a result of costimulation by CD28 and TCR, PKC- is sumoylated by SUMO1 predominantly on the sites Lys325 and Lys506. Sumoylation is important because of forming of the immunological synapse. Subsequently, PKC- phosphorylates SPAK (STE20/SPS1-related, proline alanine-rich kinase) that activates the transcription factor AP-1 (activating protein-1). PKC- also initiates the assembly of proteins Carma-1, Bcl-10 and Malt-1 by phosphorylation of Carma-1. This complex of three proteins activates the transcription factor NF-B (nuclear factor-B). Furthermore, PKC- plays a role in the activation of transcription factor NF-AT (nuclear factor of activated T cells). Thus, PKC- promotes inflammation in effector T cells. PKC- plays a role in the activation of ILC2 and contribute to the proliferation of Th2 cells. The kinase PKC- is crucial for function of Th2 and Th17. Moreover, PKC- can translocate itself to the nucleus and by phosphorylation of histons increases the accessibility of transcriptional-memory-responsive genes in memory T cells. PKC- plays a role in anti-tumor activity of NK cells. It was observed that in mice without PKC-, MHCI-deficient tumors are more often.

## The possible application of its inhibitors
Properties of PKC- make PKC- a good target for therapy in order to reduce harmful inflammation mediated by Th17 (mediating autoimmune diseases) or by Th2 (causing allergies) without diminishing the ability of T cells to get rid of viral-infected cells. Inhibitors could be used in T-cell mediated adaptive immune responses. Inhibition of PKC- downregulates transcription factors (NF-B, NF-AT) and cause lower production of IL-2. It was observed that animals without PKC- are resistant to some autoimmune diseases. PKC- could be a target of inhibitors in the therapy of allergies.
The problem is that inhibitors of PKC- targeting catalytic sites may have toxic effects because of low specificity (catalytic sites among PKCs are very similar). Allosteric inhibitors have to be more specif to concrete isoforms of PKC.s.

# Interactions
PRKCQ has been shown to interact with:
- AKT1
- FYN,
- GLRX3,  and
- VAV1.
PRKCQ has been shown to phosphorylate CARD11 as part of the NF-B signaling pathway.

# Inhibitors
- (R)-2-((S)-4-(3-Chloro-5-fluoro-6-(1H-pyrazolopyridin- 3-yl)pyridin-2-yl)piperazin-2-yl)-3-methylbutan-2-ol