A Conserved Gβ Binding (GBB) Sequence Motif in Ste20p/PAK Family Protein Kinases

2000 ◽  
Vol 381 (5-6) ◽  
pp. 427-431 ◽  
Author(s):  
E. Leberer ◽  
D. Dignard ◽  
D.Y. Thomas ◽  
T. Leeuw
Keyword(s):  
Map Kinase ◽  
Binding Site ◽  
Protein Kinases ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Binding Motif ◽  
Sequence Motif ◽  
Heterotrimeric G Protein ◽  
Family Protein ◽  
G Protein Coupled

Abstract Serine/threonine protein kinases of the Ste20p/PAK family are highly conserved from yeast to man. These protein kinases have been implicated in the signaling from heterotrimeric G proteins to mitogen-activated protein (MAP) kinase cascades and to cytoskeletal components such as myosin-I. In the yeast Saccharomyces cerevisiae, Ste20p is involved in transmitting the mating-pheromone signal from the βγ-subunits of a heterotrimeric G protein to a downstream MAP kinase cascade. We have previously shown that binding of the G-protein β-subunit (Gβ) to a short binding site in the non-catalytic carboxy-terminal region of Ste20p is essential for transmitting the pheromone signal. In this study, we searched protein sequence databases for sequences that are similar to the Gβ binding site in Ste20p. We identified a sequence motif with the consensus sequence S S L ϕP L I/V x ϕϕβ (x: any residue; ϕ: A, I, L, S, or T; β: basic residues) that is solely present in members of Ste20p/PAK family protein kinases. We propose that this sequence motif, which we have designated GBB (G̱β̱ ḇinding) motif, is specifically responsible for binding of Gβ to Ste20p/PAK protein kinases in response to activation of heterotrimeric G protein coupled receptors. Thus, the GBB motif is a novel type of signaling domain that serves to link protein kinases of the Ste20p/PAK family to G protein coupled receptors.

A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP kinase activation

Nature ◽  
1996 ◽  
Vol 383 (6600) ◽  
pp. 547-550 ◽  
Author(s):  
Ivan Dikic ◽  
George Tokiwa ◽  
Sima Lev ◽  
Sara A. Courtneidge ◽  
Joseph Schlessinger
Keyword(s):  
Map Kinase ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Kinase Activation ◽  
G Protein Coupled

scholarly journals Sphingosine 1-phosphate signalling through the G-protein-coupled receptor Edg-1

1998 ◽  
Vol 330 (2) ◽  
pp. 605-609 ◽  
Author(s):  
C. M. Gerben ZONDAG ◽  
R. Friso POSTMA ◽  
Ingrid VAN ETTEN ◽  
Ingrid VERLAAN ◽  
H. Wouter MOOLENAAR
Keyword(s):  
Adenylate Cyclase ◽  
Map Kinase ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Lpa Receptor ◽  
Kinase Activation ◽  
Protein Map ◽  
Mitogen Activated Protein ◽  
Sphingosine 1 Phosphate ◽  
G Protein Coupled

Sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) are structurally related lipid mediators that act on distinct G-protein-coupled receptors to evoke similar responses, including Ca2+ mobilization, adenylate cyclase inhibition, and mitogen-activated protein (MAP) kinase activation. However, little is still known about the respective receptors. A recently cloned putative LPA receptor (Vzg-1/Edg-2) is similar to an orphan Gi-coupled receptor termed Edg-1. Here we show that expression of Edg-1 in Sf9 and COS-7 cells results in inhibition of adenylate cyclase and activation of MAP kinase (Gi-mediated), but not Ca2+ mobilization, in response to S1P. These responses are specific in that (i) S1P action is not mimicked by LPA, and (ii) Vzg-1/Edg-2 cannot substitute for Edg-1. Thus the Edg-1 receptor is capable of mediating a subset of the cellular responses to S1P.

scholarly journals Identification of a Novel Family of Targets of PYK2 Related to Drosophila Retinal Degeneration B (rdgB) Protein

1999 ◽  
Vol 19 (3) ◽  
pp. 2278-2288 ◽  
Author(s):  
Sima Lev ◽  
John Hernandez ◽  
Ricardo Martinez ◽  
Alon Chen ◽  
Greg Plowman ◽  
...  
Keyword(s):  
Intracellular Calcium ◽  
Retinal Degeneration ◽  
G Protein ◽  
Binding Proteins ◽  
G Protein Coupled Receptors ◽  
Sequence Motif ◽  
Phosphoinositide Metabolism ◽  
Amino Terminal ◽  
Terminal Domain ◽  
G Protein Coupled

ABSTRACT The protein tyrosine kinase PYK2 has been implicated in signaling pathways activated by G-protein-coupled receptors, intracellular calcium, and stress signals. Here we describe the molecular cloning and characterization of a novel family of PYK2-binding proteins designated Nirs (PYK2 N-terminal domain-interacting receptors). The three Nir proteins (Nir1, Nir2, and Nir3) bind to the amino-terminal domain of PYK2 via a conserved sequence motif located in the carboxy terminus. The primary structures of Nirs reveal six putative transmembrane domains, a region homologous to phosphatidylinositol (PI) transfer protein, and an acidic domain. The Nir proteins are the human homologues of the Drosophila retinal degeneration B protein (rdgB), a protein implicated in the visual transduction pathway in flies. We demonstrate that Nirs are calcium-binding proteins that exhibit PI transfer activity in vivo. Activation of PYK2 by agents that elevate intracellular calcium or by phorbol ester induce tyrosine phosphorylation of Nirs. Moreover, PYK2 and Nirs exhibit similar expression patterns in several regions of the brain and retina. In addition, PYK2-Nir complexes are detected in lysates prepared from cultured cells or from brain tissues. Finally, the Nir1-encoding gene is located at human chromosome 17p13.1, in proximity to a locus responsible for several human retinal diseases. We propose that the Nir and rdgB proteins represent a new family of evolutionarily conserved PYK2-binding proteins that play a role in the control of calcium and phosphoinositide metabolism downstream of G-protein-coupled receptors.

scholarly journals 'Location, location, location': activation and targeting of MAP kinases by G protein-coupled receptors

2003 ◽  
Vol 30 (2) ◽  
pp. 117-126 ◽  
Author(s):  
LM Luttrell
Keyword(s):  
Map Kinase ◽  
G Protein ◽  
Tyrosine Kinases ◽  
Map Kinases ◽  
Focal Adhesions ◽  
G Protein Coupled Receptors ◽  
Cellular Growth ◽  
Substantial Impact ◽  
Kinase Activation ◽  
G Protein Coupled

A growing body of data supports the conclusion that G protein-coupled receptors can regulate cellular growth and differentiation by controlling the activity of MAP kinases. The activation of heterotrimeric G protein pools initiates a complex network of signals leading to MAP kinase activation that frequently involves cross-talk between G protein-coupled receptors and receptor tyrosine kinases or focal adhesions. The dominant mechanism of MAP kinase activation varies significantly between receptor and cell type. Moreover, the mechanism of MAP kinase activation has a substantial impact on MAP kinase function. Some signals lead to the targeting of activated MAP kinase to specific extranuclear locations, while others activate a MAP kinase pool that is free to translocate to the nucleus and contribute to a mitogenic response.

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