PROTEIN-KINASES SHARE A COMMON STRUCTURAL MOTIF OUTSIDE THE CONSERVEDCATALYTIC DOMAIN

A comparison of the sequences of the mammalian and Dictyostelium catal ytic subunits of cAMP-dependent protein kinase revealed extensive sequ ence similarities through the catalytic core and the carboxy terminal tail. The amino terminal sequences however differ dramaticaly. The lar ge difference in size, 73 kDa for the Dictyostelium enzyme versus 40 k Da is due to an extension in the N-terminus. The mouse enzyme has at i ts amino-terminus a long amphipatic helix, the A-helix, that precedes the catalytic core, covering the surface of both lobes of the enzyme. Dictyostelium does in fact, have a similar motif but it is remote from the catalytic core, in the N-terminal extension. On the basis of mole cular modeling, it is proposed that residues 77-98 correspond to a str uctural motif similar to the A-helix in mouse catalytic subunit. Seque nces encoding similar putatif motifs contiguous to the catalytic core can be recognized in many other protein kinases and is particularly pr ominent fn all of the non-receptor tyrosine kinases. In the case of Sr c, this A-helix motif appears to serve as the linker between the conse rved catalytic core and the SH2 domain. The interaction between the A- helix motif and the core is described, and the general occurence of th is structure within the protein kinase family is discussed.