Contribution of "Harvard" Scholars at NIH leading to our discovery of PAK1 and its blockers, "longevity" promoters

In an early 1970s, Bob Adelstein (1934-2024) and Tom Pollard, both graduates from Harvard Medical School, isolated myosin from human platelets. Then Tom joined Ed Korn's lab at NIH to isolate a single-headed myosin (Myosin I) from a soil amoeba, and found that actin-activation of Myosin I ATPase requires a third factor. In 1975, Bob's team then found that actin-activation of platelet myosin requires a kinase that phosphorylates the light chain of myosin. Meanwhile I joined Ed Korn's lab in 1974, and eventually found that the amoeba cofactor is myosin I heavy chain kinase, later called PAK1 (RAC/CDC42-activated kinase 1).

In 1994, Ed Manser's team at Singapore University cloned a "mammalian" PAK1 which is activated by two G proteins called RAC and CDC42. Then late 1990s, in collaboration with Ed Manser, our team in Melbourne found that PAK1 is essential for RAS-induced malignant transformation. Finally in 2007, we found that PAK1-deficient mutant of C. elegans lives 60% longer than the wild-type. Meanwhile, since the beginning of this century, we identified a series of natural or synthetic PAK1-blockers which cure cancers and many other diseases, eventually promoting our longevity.
Furthermore, around 2015, we established that inhibition of serum/MITF-dependent melanogenesis in B16F10 melanoma cells is the "quickest" screening criteria for PAK1-blockers.
Thus, we should greatly appreciate the "pioneer" contribution of two "Harvard" scholars (Bob and Tom) at NIH that was done a half-century ago...

In addition, in 2000, a Harvard's team (at Children's Hospital) led by Steve Harrison establisged a Xray-crystal structure of PAK1, facilitating the designing of PAK1-inhibitors:
Lei M, Lu W, Meng W, et al (2000).
Structure of PAK1 in an autoinhibited conformation reveals a multistage activation switch. Cell. 102(3):387-97.

Indeed, in 2002, we managed to find the "first" synthetic PAK1-inhibitor called CEP-1347, which selectively binds the "inactive" homodimer of this kinase:
Nheu TV, He H, Hirokawa Y et al (2002).
The K252a derivatives, inhibitors for the PAK/MLK kinase family selectively block the growth of RAS transformants. Cancer J. 8(4):328-36.