Ht31: the first protein kinase A anchoring protein to integrate protein kinase A and Rho signaling.
In an attempt to isolate protein kinase A anchoring proteins (AKAPs) involved in vasopressin-mediated water reabsorbtion, the complete sequence of the human AKAP Ht31 was determined and a partial cDNA of its rat orthologue (Rt31) was cloned. The Ht31 cDNA includes the estrogen receptor cofactor Brx and the RhoA GDP/GTP exchange factor proto-lymphoid blast crisis (Lbc) sequences. The Ht31 gene was assigned to chromosome 15 (region q24-q25). It encodes Ht31 and the smaller splice variants Brx and proto-Lbc. A protein of the predicted size of Ht31 (309 kDa) was detected in human mammary carcinoma and HeLa cells. Anti-Ht31/Rt31 antibodies immunoprecipitated RhoA from primary cultured rat renal inner medullary collecting duct cells, indicating an interaction between the AKAP and RhoA in vivo. These results suggest that Ht31/Rt31 represent a new type of AKAP, containing both an anchoring and a catalytic domain, which appears to be capable of modulating the activity of an interacting partner. Ht31/Rt31 have the potential to integrate Rho and protein kinase A signaling pathways, and thus, are prime candidates to regulate vasopressin-mediated water reabsorbtion.
Klussmann
E
E
Forschungsinstitut für Molekulare Pharmakologie, Campus Berlin-Buch, Berlin, Germany. klussman@fmp-berlin.de
Edemir
B
B
Pepperle
B
B
Tamma
G
G
Henn
V
V
Klauschenz
E
E
Hundsrucker
C
C
Maric
K
K
Rosenthal
W
W
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D002884:Chromosomes, Human, Pair 15; D003001:Cloning, Molecular; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007679:Kidney Medulla / Q000166:cytology; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D054758:A Kinase Anchor Proteins; C085467:AKAP13 protein, human; D048868:Adaptor Proteins, Signal Transducing; D020662:Guanine Nucleotide Exchange Factors; D015778:Minor Histocompatibility Antigens; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D020742:rhoA GTP-Binding Protein