The tyrosine kinase CSK associates with FLT3 and c-Kit receptors and regulates downstream signaling

Abstract

The tyrosine kinase CSK associates with FLT3 and c-Kit receptors and regulates downstream signaling.Uddin, Kazi; Vaapil, Marica; Agarwal, Shruti; Bracco, Enrico; Påhlman, Sven; Rönnstrand, Lars Link to publication Citation for published version (APA): Kazi, J. U., Vaapil, M., Agarwal, S., Bracco, E., Påhlman, S., & Rönnstrand, L. (2013). The tyrosine kinase CSK associates with FLT3 and c-Kit receptors and regulates downstream signaling. Cellular Signalling, 25(9), 1852 -1860 . DOI: 10.1016 /j.cellsig.2013 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal

SOCS proteins in regulation of receptor tyrosine kinase signaling

“…SOCS2 has higher affinity for the motifs pY-(I/L/V)-(I/L)-(I/V)-I and SOCS4 has higher affinity for the motifs pY-(I/L/V)-X-(I/V/S/T/G)-X [60]. Signaling through RTKs is tightly regulated by interacting proteins and very often SH2-domain containing proteins are involved in this regulation [4][5][6][7][106][107][108]. Since SH2 domain of different SOCS proteins displays specificity to the different pY consensus sequence it is expected that SOCS proteins display a degree of selectively in regulation of RTK signaling.…”

“…RTKs function to transduce signals from extracellular stimuli by inducing changes in tyrosine phosphorylation that promote the formation of signaling complexes leading to changes in biological processes. RTK are involved in many human diseases [4][5][6][7]. Overexpression or mutation of RTKs and their aberrant activation of downstream signaling pathways have been linked to the oncogenic transformation, angiogenesis, atherosclerosis, bone disorder, inflammation and diabetes.…”

Brain-Expressed X-linked (BEX) proteins in human cancers

“…Signaling downstream of FLT3 is tightly controlled by various signaling proteins which associate with FLT3 and regulate downstream signaling by propagating the signals from extracellular stimuli or diminish the signal by destabilizing the receptor. For example, association of GRB10, SLAP, SYK and CSK resulted in enhanced FLT3 signaling, while the association of SOCS6, SOCS2 and LNK suppressed FLT3 signaling by destabilizing the receptor [85][86][87][88][89][90][91][92][93][94][95]. BEX1 expression was found to be down-regulated in a group of FLT3-ITD positive AML patients [8].…”

The role of HOXB2 and HOXB3 in acute myeloid leukemia

“…While wild-type FLT3 requires its ligand FL for activation, oncogenic mutants are constitutively active. Activated FLT3 recruits SH2 domain-containing protein through phosphotyrosine residues resulting in activation of AKT, ERK, p38, and STAT5 [16][17][18][19][20].…”