Kinase Family RSKL

Kinase Classification: Group AGC: Kinase Family RSKL

RSKL are RSK-Like pseudokinases, named based on their similarity to the RSK family. Their functions are not well understood. There are two human members, RSKL1 (RPS6KC1) and RSKL2 (RPS6KL1).

Domain Structure

RSKL have a PX domain, followed by an MIT domain and then a kinase domain. There is no pkinase_C domain, nor room for it at the C terminus. Human RSKL2 is truncated at the N-terminus and lacks the PX domain. MIT domains may interact with microtubules and are found in proteins involved in vacuolar sorting and intracellular traffic. PX domains bind phosphoinositides and target proteins to the cell membrane. The sorting nexin, snx-15 is the only other human protein to have PX and MIT domains

RSKL kinase domains are catalytically inactive pseudokinases [1, 2], missing the DFG motif and catalytic loop.

Evolution

RSKL are found in all metazoans.

Functions

Human RSKL1 interacts with peroxiredoxin-3 through it's pseudokinase domain [3]. It also binds sphingosine kinase-1 and is colocalized with it on early endosomes. The endosomal localization required the PX domain. Both human RSKL proteins have been reported to bind HSP90 [4]

References

1. Manning G, Whyte DB, Martinez R, Hunter T, and Sudarsanam S. The protein kinase complement of the human genome. Science. 2002 Dec 6;298(5600):1912-34. DOI:10.1126/science.1075762 |
2. Manning G, Plowman GD, Hunter T, and Sudarsanam S. Evolution of protein kinase signaling from yeast to man. Trends Biochem Sci. 2002 Oct;27(10):514-20. DOI:10.1016/s0968-0004(02)02179-5 |
3. Liu L, Yang C, Yuan J, Chen X, Xu J, Wei Y, Yang J, Lin G, and Yu L. RPK118, a PX domain-containing protein, interacts with peroxiredoxin-3 through pseudo-kinase domains. Mol Cells. 2005 Feb 28;19(1):39-45.
4. Taipale M, Krykbaeva I, Koeva M, Kayatekin C, Westover KD, Karras GI, and Lindquist S. Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition. Cell. 2012 Aug 31;150(5):987-1001. DOI:10.1016/j.cell.2012.06.047 |