RHOA, RHOB, RHOC and RAC1 bind PKN1, PKN2 or PKN3

Stable Identifier
Homo sapiens
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Each protein kinase C related kinase - PKN1 (PRK1), PKN2 (PRK2) and PKN3 (PRK3) - possesses three RHO binding motifs known as HR1 (REM) domains - HR1a (REM1), HR1b (REM2) and HR1c (REM3) located at the N-termini of PKN1, PKN2 and PKN3. These domains mediate the binding of each kinase to any of the three RHO family GTPases: RHOA, RHOB and RHOC. HR1 domains of PKN1, PKN2 and PKN3 contain anti-parallel coiled-coil finger (ACC finger) folds (Maesaki et al. 1999, Hutchinson et al. 2011, Hutchinson et al. 2013). RHO GTPase RAC1 also binds and activates PKN1 (Owen et al. 2003, Modha et al. 2008), with the interaction involving HR1a and HR1b RHO-binding motifs of PKN1 and the polybasic region of RAC1, and it also binds to PKN2 (Zong et al. 1999). Binding of RAC1 to PKN3 is likely, based on sequence similarity, but has not been experimentally investigated.

Literature References
PubMed ID Title Journal Year
14514689 Molecular dissection of the interaction between the small G proteins Rac1 and RhoA and protein kinase C-related kinase 1 (PRK1)

Mott, HR, Owen, D, Chirgadze, DY, Nietlispach, D, Brosnan, CE, Parker, PJ, Lowe, PN, Blundell, TL

J. Biol. Chem. 2003
21351730 Mutational analysis reveals a single binding interface between RhoA and its effector, PRK1

Mott, HR, Owen, D, McLaughlin, SH, Hutchinson, CL, Lowe, PN

Biochemistry 2011
24128008 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

Mott, HR, Owen, D, McLaughlin, SH, Hutchinson, CL, Lowe, PN

Biochemistry 2013
10619026 The structural basis of Rho effector recognition revealed by the crystal structure of human RhoA complexed with the effector domain of PKN/PRK1

Kaibuchi, K, Kuroda, S, Hakoshima, T, Shimizu, T, Ihara, K, Maesaki, R

Mol. Cell 1999
9988689 Loop 6 of RhoA confers specificity for effector binding, stress fiber formation, and cellular transformation

Raman, N, Quilliam, LA, Atkinson, SJ, Mickelson-Young, LA, Zong, H

J. Biol. Chem. 1999
18006505 The Rac1 polybasic region is required for interaction with its effector PRK1

Mott, HR, Campbell, LJ, Owen, D, Nietlispach, D, Buhecha, HR, Modha, R

J. Biol. Chem. 2008
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