Disease relevance of Pkn1

• These data imply that although resiniferatoxin-induced translocation of protein kinase C in dorsal root ganglion neurones was mainly indirect, it also caused direct activation of a protein kinase C-like kinase in these cells [1].

High impact information on Pkn1

• Paxillin phosphorylation at Ser273 localizes a GIT1-PIX-PAK complex and regulates adhesion and protrusion dynamics [2].
• Intense protein kinase C-like immunoreactivity in the neuron was observed both in the membrane and cytoplasm of the perikarya, dendrites, axons, and axon terminals, while weak immunoreaction was seen in the nuclei but almost never in the nucleoles [3].
• PI3K, phospho (p)-PKB, and PAK were co-localized to the site of apical ES in the seminiferous epithelium of the rat testis in immunohistochemistry studies [4].
• In PC12 cells, others have shown that 6-TG blocks nerve growth factor-induced neurite outgrowth and selectively inhibits the activity of protein kinase N, a partially characterized, nerve growth factor-inducible serine-threonine kinase [5].
• Our findings suggest that (a) GTPgammaS and insulin activate Rho, PI 3-kinase, and PKN, albeit by different mechanisms; (b) each of these signaling substances appears to be required for, and may contribute to, increases in glucose transport; and (c) PKC-zeta may contribute to increases in glucose transport during insulin, but not GTPgammaS, action [6].

Biological context of Pkn1

• PAK-1 has protein and peptide substrate specificities distinct from those of known protein kinase C isoforms and is insensitive to inhibition by the protein kinase C-alpha-(19-31) pseudosubstrate peptide [7].
• Partial amino acid sequences of tryptic peptides derived from both the purified 116-kDa PAK-1 holoenzyme and its active catalytic fragment reveal that the catalytic domain is most related (50-58% identity) to the protein kinase C family [7].
• Protein kinase N1 comprised one polypeptide of Mr 35,000 which underwent phosphorylation in the presence of Mg2+ + ATP [8].
• C-PKA and PKN are widely expressed enzymes and the possibility of PKN-dependent modulation of PKA in intact cells would therefore have biological implications for signal transduction mechanisms [9].
• Rho family small G-proteins Rac and Cdc42, and their immediate downstream effector p21-activated kinase (PAK), have been demonstrated to mediate important effects on the cytoskeleton that are relevant for cell migration and proliferation [10].

Anatomical context of Pkn1

• Phosphorylation by PAK is not required for the translocation of cortactin to podosomes, lamellipodia, or membrane ruffles in A7r5 smooth muscle cells [11].
• Comparative effects of GTPgammaS and insulin on the activation of Rho, phosphatidylinositol 3-kinase, and protein kinase N in rat adipocytes. Relationship to glucose transport [6].
• In the present study, immunoprecipitates of Trk NGF receptors from PC12 cells (+/- NGF treatment) were assayed for protein kinase activity by using the substrates myelin basic protein and histone HF1 under phosphorylating conditions optimal for protein kinase N and in the presence or absence of purine analogs [12].
• Since a PKN-like activity is modulated in several cell lines by cAMP analogs and this activation requires the activity of cAMP-dependent protein kinase, the aim of the present work is to investigate possible interactions between PKN and C-PKA [9].
• Protein kinase C-like activity was found to be present in astrocytes prepared from rat neocortex and maintained in culture [13].

Associations of Pkn1 with chemical compounds

• However, other acidic phospholipids, the most effective being cardiolipin, activate PAK-1 to a similar extent as trypsin [7].
• Phosphatidylserine, diacylglycerol, and phorbol ester do not activate PAK-1 toward the S6 peptide substrate [7].
• The analogue 6-thioguanine (6-TG) has been shown to inhibit with high specificity protein kinase N (PKN), a serine/threonine protein kinase activated by NGF in several cellular systems [14].
• The analog 6-thioguanine has thus far been shown to inhibit only protein kinase N, an NGF-activated protein kinase, whereas 2-aminopurine also blocks other kinases [12].
• Protein kinase N (PKN) is a serine/threonine protein kinase rapidly activated by nerve growth factor (NGF) and other agents in various cell lines [9].

Other interactions of Pkn1

• The general S6 peptide substrate determinants for liver PAK-1 resembled those for brain protein kinase C and another major liver PAK, termed PAK-2 [15].
• The substrate specificity determinants of a protease-activated protein kinase from rat liver, termined PAK-1, have been investigated using peptide analogues of the ribosomal protein S6 sequence: Ala229-Lys-Arg-Arg-Arg-Leu-Ser-Ser-Leu-Arg-Ala-Ser-Thr-Ser-Lys- Ser244 [15].

References