The genetics of Pak

Abstract

p21-activated kinases (Paks) are a highly conserved family of enzymes that bind to and are activated by small GTPases of the Cdc42 and Rac families. With the notable exception of plants, nearly all eukaryotes encode one or more Pak genes, indicating an ancient origin and important function for this family of enzymes. Genetic approaches in many different experimental systems, ranging from yeast to mice, are beginning to decipher the different functions of Paks. Although some of these functions are unique to a given organism, certain common themes have emerged, such as the activation of mitogen-activated protein kinase (MAPK) cascades and the regulation of cytoskeletal structure through effects on the actin and tubulin cytoskeletons.

Expansion of BCR/ABL1+ cells requires PAK2 but not PAK1

“…PAKs have been well described to integrate signals from the environment to mediate cell adhesion, cytoskeletal architecture, and proliferation (Hofmann et al , 2004; Kumar et al , 2006; Li et al , 2011; Radu et al , 2014; Rane & Minden, 2014). We tested the requirement for PAK1 and PAK2 in colony formation and performed methylcellulose assays.…”

“…The p21‐activated kinases (PAKs) are conserved non‐receptor serine/threonine kinases integrating a variety of signalling pathways in biological processes, such as proliferation, apoptosis, cytoskeletal structure, and cellular motility (Hofmann et al , 2004; Kumar et al , 2006; Radu et al , 2014; Rane & Minden, 2014). PAKs are divided into group I PAKs (PAK1, PAK2, and PAK3) and group II PAKs (PAK4, PAK5, and PAK6) based on their sequence, function, and regulation.…”

“…PAKs act downstream of oncoproteins as regulators of tumour‐specific signalling pathways (Hofmann et al , 2004; Kumar et al , 2006; Radu et al , 2014; Rane & Minden, 2014). In human cancer, PAK1 is the most frequently described and studied isoform (Kumar et al , 2006).…”

“…Upon loss of PAK1, mice display reduced mast cell degranulation and disturbed glucose homeostasis (Allen et al , 2009; Wang et al , 2011; Rane & Minden, 2014). Mice deficient for PAK2 die on embryonic day E8.5 due to defects in endothelial development (Hofmann et al , 2004; Radu et al , 2015). In adult mice, conditional deletion of PAK2 led to increased vascular permeability (Radu et al , 2015).…”

A RHOse by any other name: a comparative analysis of animal and plant Rho GTPases

“…The Pak (p21-activated kinase) kinases are a family of CRIB motif-containing serine-threonine kinases that phosphorylate a wide variety of substrate proteins upon binding of activated Rac or Cdc42 [82,83]. Pak kinases participate in regulation of gene expression through MAP kinase pathways, and organization of both actin and microtubule cytoskeleton.…”