A brief history of our PAK research "for improving our QOL and longevity"

The dawn of our PAK research could be traced back to 1977 when our team at NIH found the very first member of PAK (RAC/CDC42-activated kinase) family called "myosin I heavy chain kinase" (MHCK)  in a soil amoeba (1). The F-actin-induced activation of ATPase activity of this myosin requires this kinase that phosphorylates the heavy chain. In other words this kinase is essential for the acto-myosin-based cell motility/migration (so-called  "amoeboid movement").

Around 1994, a similar kinase was cloned by Ed Manser in mammals, and coined PAK1, for p21 (RAC/CDC42)-activated kinase 1 (2).  A few years later, PAK1 was found by us and others to be essential for the RAS-induced malignant transformation of normal cells. Since then (around the turn of century), PAK1 has been the major target for developing anti-cancer drugs. Interestingly, PAK1 is not essential for the growth of normal cells. Thus, unlike the conventional anti-cancer drugs (DNA/RNA/microtubule poisons), PAK1-blockers would not cause any side effect.

More recently, PAK1 was found to be essential for many other diseases such as Alzheimer's diseases (AD), diabetes (type 2), obesity, hypertension, a variety of inflammatory and infectious diseases, as well as neuronal diseases/disorders such as epilepsy, depression, schizophrenia, autism and even headache. Furthermore, a few years ago, we revealed that PAK1-deficient mutant (RB689) of C. elegans lives significantly (by more than 50%) longer than the wild-type (3).

Thus, there is no doubt that PAK1-blockers (synthetic or natural) would have a potentially "huge"  market value in pharmaceuticals. Furthermore, this year our team at "PAK Research Center" in Okinawa found that PAK1 is essential for melanogenesis in skin cells as well. Among the best known natural PAK1-blockers is a bee product called "propolis", and it was recently found to promote hair growth in vivo. Thus, these PAK1-blockers would gain an additional attraction from cosmetics industry for skin-whitening and therapy of hair loss （alopecia).

References:

１．Maruta, H. and Korn, E.D. Acanthamoeba cofactor protein is a heavy chain kinase required for actin activation of the Mg2+-ATPase activity of Acanthamoeba myosin I.  J  Biol  Chem. 1977, 252, 8329-32.

２．Manser, E., Leung, T., Salihuddin, H., Zhao, ZS. et al. A brain Ser/ Thr protein kinase activated by Cdc42 and Rac1. Nature. 1994, 367, 40-6.
３．Yanase S, Luo Y, Maruta H. PAK1-deficiency/down-regulation Reduces Brood Size, Activates HSP16.2 Gene and Extends Lifespan in C. elegans. Drug Dev Ther. 2013, 7: 29-35.