------------------------------------------------------------------------------ specificity among alpha, beta, gamma gamma subclasses I: 1,c,11 (farnesyl,C15) II: 2,3,4,7,12 (geranylgeranyl,C20) III: 5,10 (geranylgeranyl,C20) ------------------------------------------------------------------------------ alphao binds gamma2 > gamma1, mediated by Nterm 15 residues of gamma2; gamma2 prenylation required for association with alphao Rahmatullah et al. JBC 270(7):2946 (1995) Rahmatullah and Robishaw JBC 269(5):3574 (1994) gamma carboxymethylation in beta1-gamma2, beta2-gamma3, and beta2-gamma7 enhances interaction with alphai2, alphai3 (incr PTX modification) but not membrane localization Rosenberg et al. Cellular Signalling 10:131 (1998) gamma12 (unlike others) is a substrate of PKC; phosphorylation (probably at Ser1, maybe at Ser2) increases affinity for alphao,i2 Morishita et al. JBC 270(49):29469 (1995) yeast 2-hybrid reporter activity (probably should not interpret strictly quantitatively as relative affinities) beta1 beta2 beta3 beta4 beta5 gamma1 4 3 <1 <1 <1 gamma2 8 6 2 3 2 gamma3 18 14 7 9 11 gamma4 18 15 5 6 15 gamma5 16 14 4 5 5 gamma7 16 12 4 4 3 Yan et al. JBC 271(12):7141 (1996) beta1 beta2 beta3 gamma1 + - - gamma2 + + - gamma3 + + - gamma4 + + - gamma5 + + ND gamma7 + + ND gamma10 + + - gamma11 + - - in vitro translation, biochemical assays (trypsin, gel filt, Xlink) gamma1,2 Schmidt et al. JBC 267(20):13807 (1992) colocalization of beta1,2,3 with CAAX-mutant gamma1,2 Pronin and Gautam PNAS USA 89(13):6220 (1992) in vitro translation, trypsin assay gamma 2,4,10,11 (previous work 3,5,7) Ray et al. JBC 270(37):21765 (1995) combinations of purified beta1,2 with gamma 1,2,5,7 assayed for PTX modification of alphai1,o; inhibition of GTP hydrolysis by alphas,o,i2 Ueda et al. JBC 269(6):4388 (1994) combinations of beta1,2 with gamma 1,2,3 assayed for PTX modif of alphai1 Iniguez-Lluhi et al. JBC 267(32):23409 (1992) beta1 beta2 beta3 beta3s beta4 beta5 beta5L gamma1 + (+) - - + - - gamma2 + + + - + - - gamma3 + + (+) - + - - gamma4 + + - - + - - gamma5 + + - - + - - gamma7 + + - - + - - gamma8c + + - - + - - gamma8o + + - - + - - gamma10 + + - - + - - gamma11 + - (+) - + - - gamma12 + + + - + - - gamma13 + - (+) - + - - in vitro translation, immunoprecipitation; contrasting results in HEK293 cells: PLCbeta stim incr with beta5-gamma2/4/7/8o Dingus et al. Biochem 44:(35):11882 (2005) beta4-gamma2 15x higher affinity for alphai1 than beta4-gamma11 although both trimers are stable; beta4 may dissoc from gamma11 upon alpha activation McIntire et al. Biochemistry 45(38):11616 (2006) gamma1 selectivity against beta2 due to gamma1 residues 38-40 gamma1 EEF gamma2 ADL Lee et al. JBC 270(15):8779 (1995) previously localized to gamma1 36-49 (gamma2 33-46) Spring and Neer JBC 269(36):22882 (1994) beta1 but not beta2 binds gamma1, mediated by 210-293 region of beta Katz and Simon PNAS USA 92:1998 (1995) previously implicated multiple regions within beta 215-302 (WD's 5-6) Garritsen and Simonds JBC 269(39):24418 (1994) beta1-gamma2 association mediated by gamma2 Nterm 15-25 residues (extension of 12 residues allowed) and residues 45-59 Mende et al. JBC 270(26):15892 (1995) beta1-gamma2 association requires last 10 amino acids of beta1 Yamauchi et al. Biochem Biophys Res Comm 214:694 (1995) in bovine tissues, beta1 nonsel for gammas examined (2,3,5,12) beta2 assoc gamma2,3,12 > 5 beta4 assoc gamma5 > 12 > 2 > 3 Asano et al. JBC 274(30):21425 (1999) in bovine brain, alphai1,i2,oA is with gamma2,3,7 > 5 alphaoB gamma7 > 3 > 2 alphaoC gamma5,3 > 2 alphaoA,B,C are from same gene; splice variants B vs. A,C (thought to have same sequence but different posttranslational processing) Wilcox et al. JBC 270 (9):4189 (1995) comparison of beta1 and beta5 - beta1-gamma2 and beta2-gamma2 bind alphai1,i2,o,s,q - beta5-gamma2 only binds alphaq Fletcher et al. JBC 273(1):636 (1998) additional evidence Lindorfer et al JBC 273(5):34429 (1998) beta5's physiological partners may be (instead of or as well as gamma2) C-subfamily RGS proteins which contain GGL (G-gamma-like) domains: RGS6,7,9,11 and EGL10 Sondek and Siderovski Biochem Pharmacol 61:1329 (2001) ------------------------------------------------------------------------------