title: RAFTK/PYK2-dependent and -independent apoptosis in multiple myeloma cells.
abstract: Related Adhesion Focal Tyrosine Kinase (RAFTK; also known as Pyk2), is a member of the Focal Adhesion Kinase (FAK) subfamily and is activated by TNF alpha, UV light and increases in intracellular calcium levels. However, the function of RAFTK remains largely unknown. Our previous studies demonstrated that treatment with dexamethasone (Dex), ionizing radiation (IR), and anti-Fas mAb induces apoptosis in multiple myeloma (MM) cells. In the present study, we examined the potential role of RAFTK during induction of apoptosis in human MM cells triggered by these three stimuli. Dex-induced apoptosis, in contrast to apoptosis triggered by anti-Fas mAb or IR, is associated with activation of RAFTK. Transient overexpression of RAFTK wild type (RAFTK WT) induces apoptosis, whereas transient overexpression of Kinase inactive RAFTK (RAFTK K-M) blocks Dex-induced apoptosis. In contrast, transient overexpression of RAFTK K-M has no effect on apoptosis triggered by IR or Fas. In Dex-resistant cells, Dex does not trigger either RAFTK activation or apoptosis. Finally, interleukin-6 (IL-6), a known survival factor for MM cells, inhibits both activation of RAFTK and apoptosis of MM.1S cells triggered by Dex. Our studies therefore demonstrate Dex-induced RAFTK-dependent, and IR or Fas induced RAFTK-independent apoptotic signaling cascades in MM cells.
authors.affiliation: Department of Adult Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: D
authors.initials: D
authors.lastname: Chauhan
authors.forename: T
authors.initials: T
authors.lastname: Hideshima
authors.forename: P
authors.initials: P
authors.lastname: Pandey
authors.forename: S
authors.initials: S
authors.lastname: Treon
authors.forename: G
authors.initials: G
authors.lastname: Teoh
authors.forename: N
authors.initials: N
authors.lastname: Raje
authors.forename: S
authors.initials: S
authors.lastname: Rosen
authors.forename: N
authors.initials: N
authors.lastname: Krett
authors.forename: H
authors.initials: H
authors.lastname: Husson
authors.forename: S
authors.initials: S
authors.lastname: Avraham
authors.forename: S
authors.initials: S
authors.lastname: Kharbanda
authors.forename: K C
authors.initials: KC
authors.lastname: Anderson
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D004789:Enzyme Activation; D051418:Focal Adhesion Kinase 2; D006801:Humans; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011839:Radiation, Ionizing; D014407:Tumor Cells, Cultured
chemical_list: D003907:Dexamethasone; D011505:Protein-Tyrosine Kinases; D051418:Focal Adhesion Kinase 2