Structure and Function of the Pertussis-Toxin-Insensitive G_z Protein

Abstract

G_z is the only pertussis-toxin-insensitive member of the inhibitory G protein subfamily. The unique pattern of tissue distribution of G_z suggests it may carry out tissue-specific functions, albeit it appears to share the same profile of G-protein-coupled receptors with G_i. The knowledge of the structural elements of α_z for receptor coupling and specificity has been enriched by constructing chimeric molecules. Biochemical characteristics of α_z are considerably different from other G protein α-subunits. The regulation of the GTP hydrolysis activity of α_z by various GTPase-activating proteins and the functional impact of the PKC-mediated phosphorylation of α_z are discussed. Different routes of signaling pathways that G_z could engage in have been explored. Furthermore, the possible involvement of G_z in retrograde axonal transport and various immune responses shed lights in understanding the physiological importance of G_z.

Pertussis toxin treatment prevents 5-HT5a receptor-mediated inhibition of cyclic AMP accumulation in rat C6 glioma cells

“…To date, the G i family of inhibitory G proteins consists of at least nine subtypes, including G i1-3 , G z , and G o1,2 (Hildebrandt, 1997). All members of the G i family of inhibitory G proteins exhibit sensitivity to pertussis toxin, except for the inhibitory G protein G z , which lacks a cysteine residue required for pertussis toxin binding (Ho and Wong, 1998). This rules out an involvement of G z in the results presented herein.…”

Evidence That Gz-Proteins Couple to Hypothalamic 5-HT1AReceptorsIn Vivo

“…Cotransfection experiments in cell lines indicate that G zproteins can couple to a variety of receptors such as -and ␦-opioid, ␣ 2 -adrenergic, dopamine-D 2 , adenosine-A 1 , and 5-HT 1A receptors (Ho and Wong, 1998). However, because G zprotein is expressed in large quantities in these cell lines, coupling of G z -protein to a receptor subtype might not be of physiological significance.…”

Involvement of signal transducing GTP‐binding proteins in renal artery α1‐adrenoceptor mediated smooth muscle contraction

“…However, as the phenylephrine-induced contraction could not be abolished by pertussis or cholera toxin, other toxin-insensitive mechanisms must be involved (e.g. G Q , G 11, G P , G Z or G 12 ) [9,[12][13][14]28]. All a 1 -adrenoceptor subtypes couple to pertussis toxin-insensitive G-proteins of the G Q /G 11 -family, thus activating phospholipase C, known to convey smooth muscle contraction via the generation of further second messengers [4,16,29].…”

“…Furthermore, it can activate voltagedependent Ca 2+ channels [8]. G-proteins of the G I /G O -family are mainly pertussis toxinsensitive, although one protein of this family is known to be resistant, termed G Z [9,13,14]. G I (existing as G I1 , G I2 and G I3 ) inhibits adenylyl cyclase, activates phospholipase C and activates Ca 2+ channels [6,8,15].…”

“…G O inhibits voltage-dependent Ca 2+ channels [8,15]. Other G-proteins (G K , G Z , G 12 , G Q , G 11 , G 14 , G 16 , G P , G T1 and G T2 , G H , small G-proteins) also influence intracellular effector systems like adenylyl cyclase, phospholipase C, protein kinase C, ion channels, cell growth, mitogen-activated protein kinase pathways and others, depending on the cell type [4,6,[8][9][10][12][13][14]16].…”