Linked Life Data

15147171

Source:http://linkedlifedata.com/resource/pubmed/id/15147171

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2004-5-18
pubmed:abstractText
Protein kinases control many cellular processes via the ATP-dependent phosphorylation of specific amino acids on target proteins. Despite the availability of the three-dimensional structures of a variety of protein kinases, it has been particularly difficult to explain how noncatalytic domains removed from the active site regulate catalytic function. In this review, we describe how solution methodologies complement the available structural data and help explain how protein kinases may utilize medium-to-long-range effects to regulate substrate phosphorylation. For illustration, two protein kinases, cAMP-dependent protein kinase and the C-terminal Src kinase, are presented as paradigms for the serine/threonine- and tyrosine-specific families. While active-site residues provide an optimal environment for fast phosphoryl group transfer in these and other kinases, the overall rate of protein phosphorylation is limited by nucleotide binding and associated structural changes. Hydrogen-deuterium exchange studies reveal that nucleotide binding induces changes that radiate from a central structural assembly composed of the catalytic loop, glycine-rich loop, and helix alpha C to unique peripheral regions inside and outside the kinase core. This collection of conserved and unique elements delivers information from the active site to distal regions and possibly provides information flow back to the active site. This "push-pull" hypothesis offers a means for understanding how protein kinases can be regulated by protein-protein interactions far from the active site.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0001-4842
pubmed:author
pubmed:issnType
Print
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
304-11
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Communication pathways between the nucleotide pocket and distal regulatory sites in protein kinases.
pubmed:affiliation
Department of Pharmacology, University of California, San Diego, La Jolla, California 92093-0506, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.