Molecular Glue: Kinase Anchoring and Scaffold Proteins

Abstract

pathway proceeds from the membrane bound guanine nucleotide-binding protein Ras, through the se-Vollum Institute, Oregon Health Sciences University quential activation of the cytoplasmic serine/threonine Mail Code L474 kinases Raf, MAP-kinase kinase (MEK), and MAP kinase Portland Oregon, 97201-3098 (MAPK) and leads to specific gene expression in the nucleus. In the budding yeast S. cerevisae, there are at

Organelle-specific Targeting of Protein Kinase AII (PKAII)

“…Together, conservation of N-terminal sequence, exclusive association of wild type S-AKAP84 with mitochondria, and mislocalization of the N-terminally-truncated anchor protein indicate that targeting of RII subunits to the outer mitochondrial membrane is governed principally by a segment of S-AKAP84 composed of amino acid residues 1-30. The destruction of S-AKAP84 epitopes and RII binding activity 3 by external protease demonstrates that the RII-tethering site is located in the cytoplasm adjacent to the mitochondrial surface. The demonstration that expression of S-AKAP84 elicits association of endogenous RII subunits with mitochondria in H547.1 cells (Fig.…”

“…Type II isoforms of cAMP-dependent protein kinase (PKAII␣ and PKAII␤) 1 are attached to cytoskeleton or organelles via binding of their regulatory subunits (RII␣, RII␤) with protein kinase A anchor proteins (AKAPs) (1)(2)(3). Prototypic neuronal anchor proteins (bovine AKAP75 and its human (AKAP79) and rat (AKAP150) homologs) have a conserved binding site for RII subunits and domains that non-covalently link AKAP⅐PKAII complexes to the dendritic cytoskeleton of neurons and the cortical actin cytoskeleton of non-neuronal cells (4 -9).…”

cDNA cloning of a novel human gene NAKAP95, neighbor of A-kinase anchoring protein 95 (AKAP95) on chromosome 19p13.11–p13.12 region

“…The main intracellular target for cAMP in mammalian cells is cAMPdependent protein kinase (PKA or A-kinase). PKA type II is directed to different subcellular loci through interaction of the RII subunits with A-kinase anchoring proteins (AKAPs) (Scott and Macartney, 1994;Rubin 1994;Hausken and Scotte, 1996;Faux and Scott 1996). A number of different AKAPs which direct different compartmentalizations have been found: AKAP79/75 direct the RII to postsynaptic densities and cortical actin (Carr et al 1992;Li et al 1996), AKAP250/ Gravin to filopodia (Nauert et al 1997), AKAP350 to centrosomes (Schmidt et al 1999), AKAP100 to sarcoplasmic reticulum (McCartney et al 1995), AKAP220 to peroxisome (Lester et al 1996), AKAP85 to Golgi apparatus (Keryer et al 1993), and AKAP84/149 to mitochondria (Chen et al 1997).…”

Scaffold proteins may biphasically affect the levels of mitogen-activated protein kinase signaling and reduce its threshold properties

“…At least one property of a MAPK cascade that permits its consideration as a separate module in the signal transduction pathway is the existence of scaffold proteins (4)(5)(6). These proteins have been proposed to serve as organizing centers for signal transduction because they can bind several members of a signaling cascade to form a multimolecular complex.…”