An anchoring factor targets protein phosphatase 2A to brain microtubules.
Protein phosphatase 2A (PP2A) is a ubiquitously expressed serine/threonine phosphatase composed of a heterodimeric core enzyme that associates with a variety of regulatory subunits. A fraction of brain PP2A associates with microtubules and may play a role in regulating phosphorylation of microtubule-associated proteins. We examined the isoform specificity and the mechanism involved in the association of PP2A with brain microtubules. Only the R2alpha (B/PR55alpha) and R2beta (B/PR55beta) regulatory subunits associated with endogenous neural microtubules. Neither the R2gamma (B/PR55gamma) nor members of the R5 (B'/PR56) family of regulatory subunits co-sedimented with microtubules, although abundant amounts of these proteins were detected in brain. The efficient association of PP2A with microtubules in vitro was dependent on an anchoring activity present in a brain protein fraction containing microtubule-associated and microtubule-interacting proteins. Anchoring factor-dependent association of PP2A with microtubules was specific for the heterotrimeric form of PP2A. The core dimer and the isolated subunits of PP2A had very little affinity for microtubules. Characterization of a fraction enriched in the anchoring factor showed that the activity was a heat labile protein that does not correspond to classical microtubule-associated proteins. The anchoring factor associated with microtubules independently of PP2A. These results indicate the association of PP2A with microtubules can be mediated by an anchoring factor that interacts in an isoform-specific manner with heterotrimeric forms of the phosphatase.
Price
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NE
Department of Pharmacology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235-9041, USA.
Wadzinski
B
B
Mumby
M C
MC
D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D002417:Cattle; D002460:Cell Line; D005591:Chemical Fractionation; D006358:Hot Temperature; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D054648:Protein Phosphatase 2; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D014020:Tissue Extracts / Q000737:chemistry
D007527:Isoenzymes; D008869:Microtubule-Associated Proteins; D011994:Recombinant Proteins; D014020:Tissue Extracts; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2