RHO GTPases activate PKNs

Hutchinson CL, Lowe PN, McLaughlin SH, Mott HR, Owen D. Differential binding of RhoA, RhoB, and RhoC to protein kinase C-related kinase (PRK) isoforms PRK1, PRK2, and PRK3: PRKs have the highest affinity for RhoB. Biochemistry. 2013 Nov 12;52(45):7999–8011. doi: 10.1021/bi401216w. PMID: 24128008.; Collazos A, Michael N, Whelan RD, Kelly G, Mellor H, Pang LC, Totty N, Parker PJ. Site recognition and substrate screens for PKN family proteins. Biochem J. 2011 Sep 15;438(3):535–43. doi: 10.1042/bj20110521. PMID: 21749319.; Hutchinson CL, Lowe PN, McLaughlin SH, Mott HR, Owen D. Mutational analysis reveals a single binding interface between RhoA and its effector, PRK1. Biochemistry. 2011 Apr 12;50(14):2860–9. doi: 10.1021/bi200039u. PMID: 21351730.; Dettori R, Sonzogni S, Meyer L, Lopez-Garcia LA, Morrice NA, Zeuzem S, Engel M, Piiper A, Neimanis S, Frödin M, Biondi RM. Regulation of the Interaction between Protein Kinase C-related Protein Kinase 2 (PRK2) and Its Upstream Kinase, 3-Phosphoinositide-dependent Protein Kinase 1 (PDK1). Journal of Biological Chemistry. 2009 Oct;284(44):30318–27. doi: 10.1074/jbc.m109.051151.; Kato T, Gotoh Y, Hoffmann A, Ono Y. Negative regulation of constitutive NF-kappaB and JNK signaling by PKN1-mediated phosphorylation of TRAF1. Genes Cells. 2008 May;13(5):509–20. doi: 10.1111/j.1365-2443.2008.01182.x. PMID: 18429822.; Modha R, Campbell LJ, Nietlispach D, Buhecha HR, Owen D, Mott HR. The Rac1 Polybasic Region Is Required for Interaction with Its Effector PRK1. Journal of Biological Chemistry. 2008 Jan;283(3):1492–500. doi: 10.1074/jbc.m706760200.; Owen D, Lowe PN, Nietlispach D, Brosnan CE, Chirgadze DY, Parker PJ, Blundell TL, Mott HR. Molecular Dissection of the Interaction between the Small G Proteins Rac1 and RhoA and Protein Kinase C-related Kinase 1 (PRK1). Journal of Biological Chemistry. 2003 Dec;278(50):50578–87. doi: 10.1074/jbc.m304313200.; Torbett NE, Casamassima A, Parker PJ. Hyperosmotic-induced Protein Kinase N 1 Activation in a Vesicular Compartment Is Dependent upon Rac1 and 3-Phosphoinositide-dependent Kinase 1. Journal of Biological Chemistry. 2003 Aug;278(34):32344–51. doi: 10.1074/jbc.m303532200.; Misaki K, Mukai H, Yoshinaga C, Oishi K, Isagawa T, Takahashi M, Ohsumi K, Kishimoto T, Ono Y. PKN delays mitotic timing by inhibition of Cdc25C: possible involvement of PKN in the regulation of cell division. Proc Natl Acad Sci U S A. 2001 Jan 02;98(1):125–9. PMID: 11134534; PMCID: PMC14555.; Hamaguchi T, Ito M, Feng J, Seko T, Koyama M, Machida H, Takase K, Amano M, Kaibuchi K, Hartshorne DJ, Nakano T. Phosphorylation of CPI-17, an Inhibitor of Myosin Phosphatase, by Protein Kinase N. Biochemical and Biophysical Research Communications. 2000 Aug;274(3):825–30. doi: 10.1006/bbrc.2000.3225.; Flynn P, Mellor H, Casamassima A, Parker PJ. Rho GTPase Control of Protein Kinase C-related Protein Kinase Activation by 3-Phosphoinositide-dependent Protein Kinase. Journal of Biological Chemistry. 2000 Apr;275(15):11064–70. doi: 10.1074/jbc.275.15.11064.; Maesaki R, Ihara K, Shimizu T, Kuroda S, Kaibuchi K, Hakoshima T. The structural basis of Rho effector recognition revealed by the crystal structure of human RhoA complexed with the effector domain of PKN/PRK1. Mol Cell. 1999 Nov;4(5):793–803. doi: 10.1016/s1097-2765(00)80389-5. PMID: 10619026.; Yoshinaga C, Mukai H, Toshimori M, Miyamoto M, Ono Y. Mutational Analysis of the Regulatory Mechanism of PKN: The Regulatory Region of PKN Contains an Arachidonic Acid-Sensitive Autoinhibitory Domain. Journal of Biochemistry. 1999 Sep 01;126(3):475–84. doi: 10.1093/oxfordjournals.jbchem.a022476.; Zong H, Raman N, Mickelson-Young LA, Atkinson SJ, Quilliam LA. Loop 6 of RhoA Confers Specificity for Effector Binding, Stress Fiber Formation, and Cellular Transformation. Journal of Biological Chemistry. 1999 Feb;274(8):4551–60. doi: 10.1074/jbc.274.8.4551.; Matsuzawa K, Kosako H, Inagaki N, Shibata H, Mukai H, Ono Y, Amano M, Kaibuchi K, Matsuura Y, Azuma I, Inagaki M. Domain-Specific Phosphorylation of Vimentin and Glial Fibrillary Acidic Protein by PKN. Biochemical and Biophysical Research Communications. 1997 May;234(3):621–5. doi: 10.1006/bbrc.1997.6669.; Mukai H, Toshimori M, Shibata H, Takanaga H, Kitagawa M, Miyahara M, Shimakawa M, Ono Y. Interaction of PKN with alpha-actinin. J Biol Chem. 1997 Feb 21;272(8):4740–6. doi: 10.1074/jbc.272.8.4740. PMID: 9030526.; Palmer RH, Dekker LV, Woscholski R, Le Good JA, Gigg R, Parker PJ. Activation of PRK1 by phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate. A comparison with protein kinase C isotypes. J Biol Chem. 1995 Sep 22;270(38):22412–6. doi: 10.1074/jbc.270.38.22412. PMID: 7673228.

Metabolites

CO2

Formula: CO2 (43.98983)

CAS ID: 124-38-9

Formaldehyde

Formula: CH2O (30.0105642)

CAS ID: 50-00-0

H2O

Formula: H2O (18.0105642)

CAS ID: 7732-18-5

Oxygen

Formula: O2 (31.98983)

CAS ID: 7782-44-7

2-oxoglutarate(2-)

Formula: C5H4O5 (144.00587339999998)

CAS ID: 64-15-3

succinate(2-)

Formula: C4H4O4 (116.01095839999999)

CAS ID: 56-14-4

ATP(4-)

Formula: C10H12N5O13P3 (502.9644492)

CAS ID:

GTP(4-)

Formula: C10H12N5O14P3 (518.9593642)

CAS ID: 86527-72-2

ADP(3-)

Formula: C10H12N5O10P2 (424.0059412)

CAS ID:



Enzyme

EC Number name full name note
1.14.11.-
1.14.11.65 [histone H3]-dimethyl-L-lysine9 demethylase [histone H3]-N6,N6-dimethyl-L-lysine9,2-oxoglutarate:oxygen oxidoreductase
1.14.11.66 [histone H3]-trimethyl-L-lysine9 demethylase [histone H3]-N6,N6,N6-trimethyl-L-lysine9,2-oxoglutarate:oxygen oxidoreductase
1.14.99.66 [histone H3]-N6,N6-dimethyl-L-lysine4 FAD-dependent demethylase [histone H3]-N6,N6-dimethyl-L-lysine4:acceptor oxidoreductase (demethylating)
2.7.11.1 non-specific serine/threonine protein kinase ATP:protein phosphotransferase (non-specific)
2.7.11.13 protein kinase C ATP:protein phosphotransferase (diacylglycerol-dependent)
3.1.3.16 protein-serine/threonine phosphatase protein-serine/threonine-phosphate phosphohydrolase
3.1.3.48 protein-tyrosine-phosphatase protein-tyrosine-phosphate phosphohydrolase
3.1.3.53 [myosin-light-chain] phosphatase [myosin-light-chain]-phosphate phosphohydrolase


Proteins

Protein ID name full name