High impact information on PRK1

• Thus, we revealed tight phosphoregulation of an intrinsically dynamic, actin patch-related process, and propose that Prk1p negatively regulates the actin assembly-stimulating activity of endocytic proteins [1].
• The suppression of pan1-4 by prk1 requires the presence of mutant Pan1p [2].
• Regulation of the actin cytoskeleton organization in yeast by a novel serine/threonine kinase Prk1p [2].
• By screening for mutations that can suppress the temperature sensitivity of a pan1 mutant (pan1-4), a novel serine/threonine kinase Prk1p is now identified as a new factor regulating the actin cytoskeleton organization in yeast [2].
• Ark1p and a second yeast protein, Prk1p, contain NH2-terminal kinase domains that are 70% identical [3].

Biological context of PRK1

• Consistent with its role in the regulation of actin cytoskeleton, Prk1p localizes to the regions of cell growth and coincides with the polarized actin patches [2].
• Scd5p contains a central triple repeat (3R) motif related to a known Prk1p consensus phosphorylation site L/IxxQxTG, except that Q is replaced by T [4].
• The actin-regulating kinase Prk1p negatively regulates Scd5p, a suppressor of clathrin deficiency, in actin organization and endocytosis [4].
• A homology-based three-dimensional model of the kinase domain of Prk1p provided some structural interpretations for these substrate specificities [5].
• The characterization of the [L/I/V/M]xx[Q/N/T/S]xTG motif led to the identification of a spectrum of potential targets for Prk1p from yeast genome [5].

Anatomical context of PRK1

• Although viable, the prk1 mutant is unable to maintain an asymmetric distribution of the actin cytoskeleton at 37 degreesC [2].
• In contrast to p42MAPK, activation of JNK/SAPK in Xenopus oocyte extracts was induced by both the yeast Ste20 and Shk1 kinases, as well as by mammalian Pak1 [6].
• We also demonstrate that a null mutation lacking the PAK family member myosin I heavy chain kinase (MIHCK) shows mild chemotaxis defects, including the formation of lateral pseudopodia [7].
• PAKc contains a Rac-GTPase binding (CRIB) and autoinhibitory domain, a PAK-related kinase domain, an N-terminal phosphatidylinositol binding domain, and a C-terminal extension related to the Gbetagamma binding domain of Saccharomyces cerevisiae Ste20, the latter two domains being required for PAKc transient localization to the plasma membrane [7].
• Budding yeast Pkc1p, a protein kinase C-like enzyme involved in cell wall biosynthesis and cytoskeletal polarity, is structurally and functionally related to the Rho-associated kinases (PRK/ROCK) of mammalian cells [8].

Associations of PRK1 with chemical compounds

• Prk1p also contains a proline-rich motif near its C-terminus that is required for the proper subcellular localization of the protein [9].

Enzymatic interactions of PRK1

• In this study we demonstrate that the Scd5p 3R sequence is phosphorylated by Prk1p to negatively regulate Scd5p [4].
• In this paper we show that PAK1 has similar substrate specificity as MIHCK when assayed against synthetic substrates and that PAK1 phosphorylates the heavy chain (1 mol of P(i) per mol) and activates Acanthamoeba myosin I as MIHCK does [10].

Regulatory relationships of PRK1

• Pan1p activity is negatively regulated by Prk1 kinase phosphorylation after endocytic internalization [11].
• The Saccharomyces cerevisiae PAK (p21-activated kinase) family kinase Ste20 functions in several signal transduction pathways, including pheromone response, filamentous growth, and hyperosmotic resistance [12].
• Protein kinases of the p21-activated kinase (PAK) family bind activated Rac1 and Cdc42, and switch on mitogen-activated protein (MAP) kinase pathways; however, their roles in regulating actin cytoskeleton organization have not been clearly established [3-5] [13].
• These results suggest that Ark1p and Prk1p may be downstream effectors of signaling pathways that control actin patch organization and function [3].

Other interactions of PRK1

• Recently, members of a new kinase family, the Ark/Prk kinases, which include mammalian AAK1 and GAK as well as yeast Prk1p, Ark1p, and Akl1p, were shown to regulate components of the endocytic machinery [4].
• In this report, we identified Sla1p as another substrate for Prk1p [14].
• These results suggest that Cdc42p is in fact required for pheromone response and that interaction with the PAK Ste20p is critical for that role [15].
• The physiological substrates of the PAK/STE20 kinases are not well characterized [10].
• Distinct MAP kinase pathways in yeast share several signaling components , including the PAK Ste20 and the MAPKKK Ste11, yet signaling is specific [16].

References