Oncogenicity of PAKs and Their Substrates

The serum/PDGF-dependent "melanogenic" role of the minute level of the oncogenic kinase PAK1 in melanoma cells proven by the highly sensitive kinase assay

“…Since CREB is known to be activated by LIM kinase (22,23) which like betacatenin, is among the common direct substrates of both PAK1 and PAK4 (6,18), it is most likely that PAK1 and PAK4 share the same CREB/beta-catenin-MITF signalling pathways to activate the melanogenic enzyme genes.…”

“…Thus, it is most likely that PAK1 is involved in the activation of these melanogenic/oncogenic transcription factors in hair cells, eye irises or skin melanocytes. Indeed, at least beta-catenin is among the direct substrates of PAK1 (6). PAK1 phosphorylates beta-catenin at Ser 675 for the activation, leading to malignant transformation.…”

Herbal Therapeutics that Block the Oncogenic Kinase PAK1: A Practical Approach towards PAK1-dependent Diseases and Longevity

“…Both PAK1 and PAK4 are hyper‐activated or hyper‐expressed in a variety of solid tumors and are essential for the malignant growth of these tumors (He and Maruta, ). Oncogenic mutants of three distinct RAS genes (Ki‐RAS, Ha‐RAS and N‐RAS) present in human (and other mammals) activate both PAK1 and PAK4 (see Fig.…”

“…Thus, blocking these PAKs could prevent cancers from their metastasis. For details, see a previous review (He and Maruta, ).…”

The Assessment of Anticoagulative System: Two Natural Anticoagulants Protein C and Antithrombin III

“…Aberrant activation of RTKs often leads to malignant transformation, whereas PI3K/Axl is required for this oncogenic receptor signaling (Utermark et al, 2012). At present, the oncogenic receptors and their target antibodies (Abs) (Yang et al, 2014) strategies have been widely extended to CD44 oncogenic receptor of Hyaluronic Acid(HA) (He et al, 2013), RAGE oncogenic receptor (Radia et al, 2013;Xu et al, 2013;Wang et al, 2015;Zhang et al, 2016), the oncogenic receptor platelet-derived growth factor receptor- (PDGFR) or PDGFRa linked to the pathogenesis of myeloproliferative neoplasm or chronic leukemia (Zhu, 2017Esposito et al, 2018),cytokine IL-3/oncogenic receptor IL3R, IL-6/ IL6R-STAT3-ADAR1 (P150) oncogenic transcription factors (Teoh et al, 2020), oncogenic IL7R (Mansour et al, 2015), IL-11/IL-11 gp130 receptor pro-oncogenic signaling Ernst et al,2008, Ernst andPutoczki, 2014;Merchant, 2008) and oncogenic receptor IL17rb (Huang et al, 2017;Poultsidi et al, 2018). Targeting against a deregulated dominant oncogenic receptor such as the oncogenic Estrogen Receptor (ER) pathway (tamoxifen) (Green and Chambon, 1986;Chin et al, 2014;Singh and Kumar, 2005;Elangovan et al, 2011;Zinger et al, 2019;Ludwik et al, 2018;Veeraraghavan et al, 2014;Tilli et al, 2003;Davis, 2012;Yue et al, 2013;Hickey et al, 2021;Marx et al, 2007;Zhu, 2017, and blocking oncogenic receptor HER3/ HER2 agent trastuzumab is enough to slow tumor progression (Zhu, 2017Marx et al, 2007;De Bacco et al, 2004;Moody et al, 2015;…”