JUN is also regulated by 13 other proteins. It is therefore tempting to speculate that the real pathway may go through JUN since regulation of any of the 13 proteins by PMA would give a plausible explanation of the associations between PMA and the two pathways. Further experiments can be designed using such information to elucidate the true mechanism. In Fig 6, we plot all the proteins and pathways that are affected by PMA directly or indirectly when directionality information is taken into account, which is substantially smaller than Fig 4b. Simply from the names of some of the pathways , we can see that they should be regulated by PMA since PMA directly activates IL2 and some of the pathways are related to IL2. Manual verification of all the relationships between PMA and pathways is not a trivial task. One way is to perform a retrieval search using both PMA and a pathway name as the keyword at PubMed. Returned articles from the searches can be manually read to confirm the relationship. For those PubMed searches with no hits, searches on Google sometimes provide clues on the relationship. Again those need to be carefully followed to confirm the relationship. For instance, searching PMA and pathway, Calcineurin-regulated NFAT-dependent transcription in lymphocytes, did not return any articles in PubMed. However, we found some evidence through Google search for the association. Of course, even there is no any reported evidence for a relationship it can still be true. Another pathway we examined is muscle contraction, which is separated from PMA by four proteins. PubMed search using PMA and muscle contraction as the keywords returned 182 articles. The first article published Gefitinib customer reviews recently studied the Torin 1 cost mechanism of PKC induced muscle contraction using mouse model and reported that PKC activation by PMA increased the level of protein TRPM4, which may be responsible for the smooth muscle cell depolarization and vasoconstriction of cerebral arteries. Using the PMA network in Fig 6 containing all the human proteins, another mechanism can be hypothesized, which can be tested experimentally if a follow-up by manual literature review considers it worthwhile. In the current database, muscle contraction is associated with other 44 proteins and PMA interacts with another 8 proteins.