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.
Although the integral membrane proteins that catalyze steps in the biosynthesis of neuroendocrine peptides are known to contain routing information in their cytosolic domains, the proteins recognizing this routing information are not known. Using the yeast two-hybrid system, we previously identified P-CIP10 as a protein interacting with the cytosolic routing determinants of peptidylglycine alpha-amidating monooxygenase (PAM). P-CIP10 is a 217-kDa cytosolic protein with nine spectrin-like repeats and adjacent Dbl homology and pleckstrin homology domains typical of GDP/GTP exchange factors. In the adult rat, expression of P-CIP10 is most prevalent in the brain. Corticotrope tumor cells stably expressing P-CIP10 and PAM produce longer and more highly branched neuritic processes than nontransfected cells or cells expressing only PAM. The turnover of newly synthesized PAM is accelerated in cells co-expressing P-CIP10. P-CIP10 binds to selected members of the Rho subfamily of small GTP binding proteins (Rac1, but not RhoA or Cdc42). P-CIP10 (kalirin), a member of the Dbl family of proteins, may serve as part of a signal transduction system linking the catalytic domains of PAM in the lumen of the secretory pathway to cytosolic factors regulating the cytoskeleton and signal transduction pathways.
Alam
M R
MR
Departments of Neuroscience and Physiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Johnson
R C
RC
Darlington
D N
DN
Hand
T A
TA
Mains
R E
RE
Eipper
B A
BA
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins; D003001:Cloning, Molecular; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012333:RNA, Messenger; D051381:Rats; D016415:Sequence Alignment; D013049:Spectrin / Q000378:metabolism*; D014018:Tissue Distribution; D014162:Transfection; D020692:rab3 GTP-Binding Proteins
D002352:Carrier Proteins; D020662:Guanine Nucleotide Exchange Factors; C102365:Kalrn protein, rat; D009097:Multienzyme Complexes; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D013049:Spectrin; D006899:Mixed Function Oxygenases; C035189:peptidylglycine monooxygenase; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins