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- PAK1 (RAC/CDC42-activated kinase 1) is the major “pathogenic” kinase whose abnormal activation causes a wide variety of diseases/disorders including cancers, inflammation, malaria and pandemic viral infection including influenza, HIV and COVID-19. (Maruta & He, 2020)
Re: Chloroquine (CQ)
"In 2016, a Korean team found that the CQ up-regulates p21 (a CDK inhibitor) whose expression is suppressed by PAK1 [3,6]. More recently, a tumor-suppressing phosphatase called PTEN, that inactivates PAK1, was shown to suppresse the coronavirus-induced LLC2-dependent fibrosis (lung inflammation) . Further-more, expression of LLC2 depends on the coronavirus receptor (called ACE2 = Angiotensin-converting enzyme 2) -induced CK2/RAS-PAK1-RAF-AP1 signaling pathway [, Fig. 1 ]. These observations altogether clearly indicate the PAK1-dependency of coronaviral pathogenesis, and strongly suggest, if not proven clinically as yet, that PAK1-blockers in general could be useful for the treatment of current “pandemic” COVID-19 infection..." (Maruta & He, 2020)
Maruta H, He H - "PAK1-blockers: Potential Therapeutics against COVID-19" Med Drug Discov 100039 (2020) doi: 10.1016/j.medidd.2020.100039. Epub ahead of print. PMID: 32313880; PMCID: PMC7166201.
PAK1 is regulated via Gq/11.
"These data demonstrate that in IEC-18 cells, Ang II-dependent activation of the COX-2 promoter is mediated primarily through Gq/11 signaling via a PAK/MKK6/p38beta/CREB signaling cascade." (Pham et al., 2008)
Pham H, Vincenti R, Slice LW - "COX-2 promoter activation by AT1R-Gq-PAK-p38beta signaling in intestinal epithelial cells" Biochim Biophys Acta. 1779(6-7):408‐413 (2008) doi:10.1016/j.bbagrm.2008.05.004
"In addition to its well known involvement in Gq/11-mediated vasoconstriction and its key roles in the homeostasis of electrolyte balances, the angiotensin II type 1 (AT1) receptor activates mitogen-activated protein kinase (MAPK) and p42/44 extracellular signal-regulated kinase. The extracellular signal-regulated kinase activation is mediated by activation of p21-Ras, Raf-1, and MAPK kinase in rat vascular smooth muscle cells."(Inagami et al., 1999)
Inagami T, Eguchi S, Numaguchi K, et al - "Cross-talk between angiotensin II receptors and the tyrosine kinases and phosphatases" J Am Soc Nephrol 10 Suppl 11:S57‐S61 (1999)
ERK/MAPK - viewtopic.php?f=66&t=1914
CD42 - viewtopic.php?f=66&t=1941