Cloning and characterization of an alternatively spliced form of SR protein kinase 1 that interacts specifically with scaffold attachment factor-B

Serine/arginine protein kinases have been conserved throughout evolution an d are thought to play important roles in the regulation of mRNA processing, nuclear import, germline development, polyamine transport, and ion homeost asis. Human SRPK1, which was first identified as a kinase specific for the SR family of splicing factors, is located on chromosome 6p21.2-p21.3. We re port here the cloning and characterization of SRPK1a, which is encoded by a n alternatively processed transcript derived from the SRPK1 gene. SRPK1a co ntains an insertion of 171 amino acids at its NH2-terminal domain and is si milar to SRPK1 in substrate specificity and subcellular localization. Moreo ver, both isoforms can induce alternative splicing of human tau exon 10 in transfected cells. Using the yeast two-hybrid assay, we found that the exte nded NH2-terminal domain of SRPK1a interacts with Scaffold Attachment Facto r-B, a nuclear scaffold-associated protein. Confirmation of this interactio n was provided by in, vitro binding assays, as well as by co-immunoprecipit ation from 293T cells doubly transfected with SRPK1a and SAF-B. Our studies suggest that different SRPK family members are uniquely regulated and targ eted and thus the multiple SRPK kinases present in higher eukaryotes may pe rform specialized and differentiable functions.