FRK/PTK6 (also known as Fyn-related kinase) kinase family is a small family of intracellular Src-related tyrosine kinases, which has an exon-intron structure distinct from Src-family members. There family members have been identified for FRK/PTK6 kinase family, which are FRK/RAK, PTK6/BRK and SRMS.
Expression of FRK was originally identified in primary human breast cancer. Like Src family members, FRK has the SH2 and SH3 domains, a catalytic domain and a C-terminal regulatory domain but lacking N-terminal myristoylation/palmitoylation. Studies showed that FRK is a tumor suppressor which overexpression induces growth arrest.
PTk6 is a 451 amino acid protein, with the SH2 and SH3 domains at N-terminus and a C-terminal kinase domain. PTK6 family members do have the modifications, such as myristoylation and palmitoylation, which is unlike SRC family members. Therefore, PTK6 kinases are more flexible in the subcellular localization. PTK6 can be found in both the cytoplasm and nucleus. The known substrates of PTK6 include beta-catenin, KAP3A, Paxillin and PSF. Some other potential substrates are being validated, such as beta-tubulin, GNAS and ELJ39441/SPTY2D1. PTK6 can be activated by transcription factors, such as KLF9 and NFkB, and other activators, such as calcium, OPN, EGF and HRG. The inhibition of PTK6 activity can be regulated by inhibitors, SOCS3. The function of PTK6 is involved in differentiation, cell cycle progression, migration, angiogenesis and apoptosis.