Intracellular Targeting of Signals Carried by Cyclic AMP

Charles Rubin, Feng Doug

Research output: Contribution to journalArticlepeer-review


Mechanisms by which diffuse c.AMP signals are captured, amplified and foi ussed on distal substrate-effector proteins in highly polarized epithelial cells are not fully understood. We have cioned ( DNA that encodes six novel A kinase anchor proteins (collectively named AKAP-KL). AKAP-KL diversity is generated by alternative mRNA splicing and utilization of two translation initiation codons. AKAP-KL polypeptides are evident in lung, kidney and cerebellum, but are absent from many tissues. Different isoforms predominate in different tissues. Thus, AKAP-KL expression is differentially regulated in vivo. All A KAP-K I. isoformt, contain a 20-residue domain that, avidly binds (K/j 10 nM) regulatory subunits (RI1) of protein kinase All and is highly homologous with the RII tethering site in neuronal AKAP75. The distribution of AKAP-KL is strikingly asymmetric (polarized) in situ. Anchor protein accumulates near the inner, apical surface of highly polarized epithelium in tubules of nephrons. Hot h R1I and AKAP-KL are enriched at an intracellular site that lies just below the plasma membrane of alveolar epithelial cells in lung. AKAP-KL interacts with and modulates the structure of the aciin cytoskeleton in tran.sfected cells. We also demonstrate that the tethering domain of AKAP-KL avidly ligates Rll subunits in intact cells. AKAP-KL may be involved in (a) establishing polarity in signaling systems and (b) physically and functionally integrating PKAII isotorrns with downstream effectors in order to capture, amplify and precisely Irx us diffuse, tran.s-cellular signals carried by cAMP.

Original languageEnglish (US)
Pages (from-to)A1297
JournalFASEB Journal
Issue number8
StatePublished - Dec 1 1998

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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