Kalirin, a Cytosolic Protein with Spectrin-like and GDP/GTP Exchange Factor-like Domains That Interacts with Peptidylglycine alpha -Amidating Monooxygenase, an Integral Membrane Peptide-processing Enzyme

doi:10.1074/jbc.272.19.12667

Volume 272, Number 19, Issue of May 9, 1997 pp. 12667-12675
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Kalirin, a Cytosolic Protein with Spectrin-like and GDP/GTP Exchange Factor-like Domains That Interacts with Peptidylglycine $alpha$ -Amidating Monooxygenase, an Integral Membrane Peptide-processing Enzyme

(Received for publication, February 3, 1997, and in revised form, March 5, 1997)

M. Rashidul Alam , Richard C. Johnson , Daniel N. Darlington , Tracey A. Hand , Richard E. Mains and Betty A. Eipper

From the Departments of Neuroscience and Physiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 and the Departments of Surgery and Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201

Although the integral membrane proteins that catalyze steps in the biosynthesis of neuroendocrine peptides are known to containrouting information in their cytosolic domains, the proteins recognizingthis routing information are not known. Using the yeast two-hybridsystem, we previously identified P-CIP10 as a protein interactingwith the cytosolic routing determinants of peptidylglycine $alpha$ -amidatingmonooxygenase (PAM). P-CIP10 is a 217-kDa cytosolic protein withnine spectrin-like repeats and adjacent Dbl homology and pleckstrinhomology domains typical of GDP/GTP exchange factors. In the adultrat, expression of P-CIP10 is most prevalent in the brain. Corticotropetumor cells stably expressing P-CIP10 and PAM produce longer andmore highly branched neuritic processes than nontransfected cellsor cells expressing only PAM. The turnover of newly synthesizedPAM is accelerated in cells co-expressing P-CIP10. P-CIP10 bindsto selected members of the Rho subfamily of small GTP bindingproteins (Rac1, but not RhoA or Cdc42). P-CIP10 (kalirin), a memberof the Dbl family of proteins, may serve as part of a signal transductionsystem linking the catalytic domains of PAM in the lumen of thesecretory pathway to cytosolic factors regulating the cytoskeletonand signal transduction pathways.

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