TAM receptors: TYRO3 (T), AXL(A), MER (M)
These are a family of tyrosine kinases with 2 Ig like motifs and 2 fibronectin III motifs. They are the arms of phagocytosis used by macrophages for viral infections.
Each IFN favors a different TAM.
IFNalpha which is sent after TLR7 or TLR9 are triggered means a viral or foreign infection of the mitochondria or nucleus. Induces cells to make HLA-A and HLA-B.
IFNbeta which is sent after TLR3 which means a viral infection of the cytosol. HLA-Ds are made.
IFNgamma....tends to be made more by natural killer cells. TLR8 which when triggered makes IFNgamma often never gets through. This is the condition of a viral or foreign infection of the endoplasmic reticulum which means the HLAs may never make it to the surface.
Here is the previous post if you want references:
http://angelabiggs.blogspot.com/2017/01/tlrs-toll-like-receptors-summary.html
Now if you look at the TAMS you can see a similar pattern of expression.
IFN alpha, MER, and TLR7 /TLR9
https://arthritis-research.biomedcentral.com/articles/10.1186/ar4517
IFN beta, TYRO3, and TLR3
https://www.ncbi.nlm.nih.gov/pubmed/26085147
IFN gamma, AXL, and natural killer cells
https://www.ncbi.nlm.nih.gov/pubmed/18840707
What is interesting about this is that AXL is considered the TAM for "do not eat me" which is worn by growing neurons, placentas, and even cancer cells. Is this actually a "don't bother with phagocytosis" marker? There is nothing for the TAM to grab onto. The ER of the infected cell can't make the correct grab proteins. Because moving/growing cells would attract macrophages does the Axl stop them...almost pretending to be another macrophage?
In the state of endoplasmic reticulum infection very little GAS6 or S proteins will be visible on the surface of the infected cell.
(cytosol net) TLR3 IFN beta HLA-D (mailbox cytosol)
tyro-3 (macrophage hands)
(nuclear net) TLR7 IFN alpha HLA-A (mailbox nuclear)
(mitochondria net) TLR9 HLA-B (mailbox mitochondria)
MER (macrophage hand)
TLR-8 IFN gamma HLA-C (endoplasmic reticulum)
(endoplasmic reticulum net) AXL (macrophage hand of don't bother eating)
or Natural Killer cells
So when a net catches something foreign in this region it sends an IFN signal which causes the correct mailbox for the area to be made and the same signal tells the macrophages which arms to wear.
Pondering: what is the difference between tyro3 and mer? Do nuclear viruses require more containment ?
MER is also involved in apoptosis.
MER has been located in the nucleus.
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0031635
Does MER shut down or slow the DNA processes, like transcription, temporarily so DNA viruses can't use them?
Does Tyro3 interfere with RNA and ribosome processes since it is linked to RNA viruses of the cytosol?
Tyro3 may have a synaptic function
http://europepmc.org/articles/pmc2231337
The ribosomes at the synapse....is their translation altered on and off by tyro3?
Tyro3 was involved in the altered location of RNA
http://dmm.biologists.org/content/dmm/early/2017/01/11/dmm.027433.full.pdf
Curious possibilities:
Does MER also have a DNA transcription job because of it's link to DNA viruses?
Does tyro3 also have an RNA translation job because of it's link to RNA viruses?
Because AXL is involved with endoplasmic reticulum viruses does it therefore increase transcription to help the odds of something getting through the ER mess?
AXL has been found in Cancer and embryo genesis
http://www.clinsci.org/content/122/8/361 (AXL review)
AXL has been found to be involved with vascular repair
http://circres.ahajournals.org/content/83/7/697
In both of these states one might see an increase in transcription.
Enveloped viruses in an attempt to stop macrophages bind the TAM ligands : removing the immune response
http://www.cell.com/cell-host-microbe/abstract/S1931-3128(13)00253-9?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1931312813002539%3Fshowall%3Dtrue
http://www.cell.com/cell-host-microbe/fulltext/S1931-3128(13)00262-X
Note that all 3 TAMs bind the "growth arrest specific" gene Gas-6 and protein S
https://www.ncbi.nlm.nih.gov/pubmed/21057587
These are a family of tyrosine kinases with 2 Ig like motifs and 2 fibronectin III motifs. They are the arms of phagocytosis used by macrophages for viral infections.
Each IFN favors a different TAM.
IFNalpha which is sent after TLR7 or TLR9 are triggered means a viral or foreign infection of the mitochondria or nucleus. Induces cells to make HLA-A and HLA-B.
IFNbeta which is sent after TLR3 which means a viral infection of the cytosol. HLA-Ds are made.
IFNgamma....tends to be made more by natural killer cells. TLR8 which when triggered makes IFNgamma often never gets through. This is the condition of a viral or foreign infection of the endoplasmic reticulum which means the HLAs may never make it to the surface.
Here is the previous post if you want references:
http://angelabiggs.blogspot.com/2017/01/tlrs-toll-like-receptors-summary.html
Now if you look at the TAMS you can see a similar pattern of expression.
IFN alpha, MER, and TLR7 /TLR9
https://arthritis-research.biomedcentral.com/articles/10.1186/ar4517
IFN beta, TYRO3, and TLR3
https://www.ncbi.nlm.nih.gov/pubmed/26085147
IFN gamma, AXL, and natural killer cells
https://www.ncbi.nlm.nih.gov/pubmed/18840707
What is interesting about this is that AXL is considered the TAM for "do not eat me" which is worn by growing neurons, placentas, and even cancer cells. Is this actually a "don't bother with phagocytosis" marker? There is nothing for the TAM to grab onto. The ER of the infected cell can't make the correct grab proteins. Because moving/growing cells would attract macrophages does the Axl stop them...almost pretending to be another macrophage?
In the state of endoplasmic reticulum infection very little GAS6 or S proteins will be visible on the surface of the infected cell.
(cytosol net) TLR3 IFN beta HLA-D (mailbox cytosol)
tyro-3 (macrophage hands)
(nuclear net) TLR7 IFN alpha HLA-A (mailbox nuclear)
(mitochondria net) TLR9 HLA-B (mailbox mitochondria)
MER (macrophage hand)
TLR-8 IFN gamma HLA-C (endoplasmic reticulum)
(endoplasmic reticulum net) AXL (macrophage hand of don't bother eating)
or Natural Killer cells
So when a net catches something foreign in this region it sends an IFN signal which causes the correct mailbox for the area to be made and the same signal tells the macrophages which arms to wear.
Pondering: what is the difference between tyro3 and mer? Do nuclear viruses require more containment ?
MER is also involved in apoptosis.
MER has been located in the nucleus.
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0031635
Does MER shut down or slow the DNA processes, like transcription, temporarily so DNA viruses can't use them?
Does Tyro3 interfere with RNA and ribosome processes since it is linked to RNA viruses of the cytosol?
Tyro3 may have a synaptic function
http://europepmc.org/articles/pmc2231337
The ribosomes at the synapse....is their translation altered on and off by tyro3?
Tyro3 was involved in the altered location of RNA
http://dmm.biologists.org/content/dmm/early/2017/01/11/dmm.027433.full.pdf
Curious possibilities:
Does MER also have a DNA transcription job because of it's link to DNA viruses?
Does tyro3 also have an RNA translation job because of it's link to RNA viruses?
Because AXL is involved with endoplasmic reticulum viruses does it therefore increase transcription to help the odds of something getting through the ER mess?
AXL has been found in Cancer and embryo genesis
http://www.clinsci.org/content/122/8/361 (AXL review)
AXL has been found to be involved with vascular repair
http://circres.ahajournals.org/content/83/7/697
In both of these states one might see an increase in transcription.
Enveloped viruses in an attempt to stop macrophages bind the TAM ligands : removing the immune response
http://www.cell.com/cell-host-microbe/abstract/S1931-3128(13)00253-9?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1931312813002539%3Fshowall%3Dtrue
http://www.cell.com/cell-host-microbe/fulltext/S1931-3128(13)00262-X
Note that all 3 TAMs bind the "growth arrest specific" gene Gas-6 and protein S
https://www.ncbi.nlm.nih.gov/pubmed/21057587
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