MINIREVIEW
TEC family kinases in health and disease – loss-of-function
of BTK and ITK and the gain-of-function fusions ITK–SYK
and BTK–SYK
Alamdar Hussain
1,2,
*, Liang Yu
1,3,
*, Rani Faryal
1,2
, Dara K. Mohammad
1
, Abdalla J. Mohamed
1,4
and C. I. Edvard Smith
1
1 Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Huddinge University Hospital, Sweden
2 Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan
3 Department of Hematology, Huaian No. 1 Hospital, Nanjing Medical University, Huaian, Jiangsu, China
4 Faculty of Science (Biology), Universiti Brunei Darussalam, Gadong, Brunei Darussalam
Introduction
TEC family kinases (TFKs) evolved 600 million years
ago prior to the existence of metazoans [1] and com-
prise five members in mammals: Bruton’s tyrosine
kinase (BTK), inducible T-cell kinase (ITK), TEC,
BMX [also known as epithelial and endothelial tyro-
sine kinase (ETK)] and TXK [also known as resting
lymphocyte kinase (RLK)]. The phenotypes of loss-of-
function mutations in mammals mainly affect the
hematopoietic system, whereas, in fruit fly oogenesis,
male genital development and life span are compro-

BTK, as an immunosuppressant, whereas there is evidence that the inhibi-
tion of inducible T-cell kinase (ITK) could influence the infectivity of HIV
and also have anti-inflammatory activity. Since 2006, several patients carry-
ing a fusion protein, originating from a translocation joining genes encoding
the kinases ITK and spleen tyrosine kinase (SYK), have been shown to
develop T-cell lymphoma. We review these disease processes and also
describe the role of the N-terminal pleckstrin homology–Tec homology
(PH–TH) domain doublet of BTK and ITK in the downstream intracellular
signaling of such fusion proteins.
Abbreviations
AKT, v-akt murine thymoma viral oncogene; BTK, Bruton’s tyrosine kinase; EBV, Epstein–Barr virus; ITK, inducible T-cell kinase; NKT cell,
natural killer T cell; PH, pleckstrin homology; PKB, protein kinase B; R28C, arginine 28 mutated to cysteine; SH2, Src homology 2;
SH3, Src homology 3; SYK, spleen tyrosine kinase; TFK, TEC family kinase; TH, Tec homology; XLA, X-linked agammaglobulinemia.
FEBS Journal 278 (2011) 2001–2010 ª 2011 The Authors Journal compilation ª 2011 FEBS 2001
disease, in which TFKs are showing increasing impor-
tance, both as an underlying cause, but recently also
as potential targets for new drugs. The main emphasis
is on BTK and ITK deficiency, as well as the translo-
cation between ITK and spleen tyrosine kinase (SYK).
Very recently, the TXK ⁄ TEC loci have also been asso-
ciated with disease, namely the development of rheu-
matoid arthritis, in a genome-wide screen [8].
Mutations affecting BTK cause
X-linked agammaglobulinemia (XLA)
and provide insight into basic signaling
mechanisms
In 1992, two TFKs were already known, namely TEC
and ITK (reviewed in Ref. [1]). Even though informa-
tion was available regarding their potential function, it
was the identification of BTK, as the kinase affected in

the various domains of BTK. Mutations affecting the
R28 residue (marked in dark blue in Fig. 1) will result
in the redistribution of electrostatic charges that are
Fig. 1. Structure of PH, SH2 and kinase domains of BTK with color-
ing of residues affected by missense mutations. Top left: locations
of the missense mutation in the BTK PH domain; arginine 28 is in
dark blue, encircled in red. Bottom left: SH2 domain. Right: kinase
domain. The mutated residues are indicated in yellow, a-helices are
in cyan, b-sheets are in magenta and loops are in blue. Modified
from Valiaho et al. [19].
Fig. 2. (A) Schematic representation of BTK, ITK, SYK and the cor-
responding fusion proteins. PH, pleckstrin homology domain; TH,
Tec homology domain; SH3, Src homology 3 domain; SH2, Src
homology 2 domain; Y, linker region tyrosine (Y352); YY, activation
loop tyrosines (Y525 ⁄ Y526). (B) Graphic representation showing
that the PH–TH domain differences between BTK–SYK and ITK–
SYK fusion proteins lead to differential phosphorylation levels of
the fusion proteins themselves, as well as the downstream adapter
proteins SLP76 and BLNK, in 293T and COS7 cells. Size of red
encircled ‘P’ approximately represents the phosphorylation levels.
TEC kinases and disease A. Hussain et al.
2002 FEBS Journal 278 (2011) 2001–2010 ª 2011 The Authors Journal compilation ª 2011 FEBS
indispensible for ligand binding. Many of the muta-
tions locate to highly structurally conserved regions,
such as a-helices or b-sheets, whereas some are posi-
tioned in the connecting loops. Approximately one-
third of all mutations in the BTK gene are missense
and some of these reduce the stability of the protein.
This is exemplified by mutations in the BTK motif of
the Tec homology (TH) domain [18]. This region is

acid creating a fixed kink in a protein chain.
Similar to the situation in many other genes, CpG
dinucleotides in the BTK gene are more susceptible to
mutation, approximately by an order of magnitude
[21]. Owing to the high frequency of CpG dinucleo-
tides in arginine codons, the mutation spectrum pro-
vides a few highly significant genotype–phenotype
correlations. Thus, certain codons, such as those
encoding R13 and R288 in the PH and SH2 domains
of BTK, respectively, are permissive for missense, but
not for nonsense, changes, as there are no reported
XLA patients with an R13 or R288 substitution, but
plenty with stop codons [21]. Conversely, for other
arginine codons, corresponding to, for example, R520
and R525, located in the kinase domain, both non-
sense and missense mutations cause XLA (P < 0.001).
This provides immediate insight into potential con-
formational restrictions, as ‘tolerated’ BTK substitu-
tions, exchanging R13 or R288 for other amino acids,
presumably exist in the general population as rare,
normal variants with maintained signaling function.
To date, such rare variants have not been described,
but, owing to their expected extremely low frequency,
this outcome is anticipated. Recently, a rare variant, a
nonpathogenic mutation predicted to affect the BTK
SH3 domain by generating an A230V amino acid sub-
stitution, was reported [23]. Structural analysis shows
that this residue is located in the RT loop of the SH3
domain, which is involved in the recognition of inter-
acting partners [24].

Over the last few years, several companies have devel-
oped small-molecule inhibitors for BTK [32] and ITK
[33,34]. ITK inhibitors may potentially be used for the
treatment of inflammatory diseases [34] and, as discussed
below, may also become part of the anti-HIV therapeu-
tic arsenal. By blocking B-lymphocyte development,
BTK inhibitors could potentially replace treatment with
monoclonal antibodies directed against B-lymphocyte
surface antigens, currently a multibillion dollar market.
To this end, even after withdrawal, such monoclonals
A. Hussain et al. TEC kinases and disease
FEBS Journal 278 (2011) 2001–2010 ª 2011 The Authors Journal compilation ª 2011 FEBS 2003
continue to suppress B-lymphocyte levels for long time
periods, and it would be of great interest if the effect of
BTK inhibitors could be more quickly reversed.
A mutation affecting ITK causes
susceptibility to Epstein–Barr virus
(EBV) infection
Although a multitude of disease-causing mutations in
the BTK gene have been identified, it was only in 2009
that a spontaneous alteration in another human TFK
gene was reported, namely in the ITK gene [35]. ITK
was discovered using a degenerate PCR screen for
novel T-cell-expressed kinases [36,37]. This enzyme
serves as an important player in inflammatory disor-
ders, such as allergic asthma and atopic dermatitis
[38,39]. In this minireview series, two articles describe
the current understanding of ITK’s role in signaling
and development [40,41].
Thus, in 2009, Huck et al. [35] identified two sisters

killer T cells (NKT cells).
Even though the patients with the R335W mutation
completely lacked ITK protein, mutations in the ITK
SH2 domain may have additional effects when the pro-
tein remains stable, by acting as a dominant negative
form, or by interfering with other functional parts of
the molecule. Thus, as a functional SH2 domain is nec-
essary for enzymatic activity, it is likely that kinase
activity is also compromised in certain mutants desta-
bilizing the SH2 domain in TFKs [43,44]. So far, more
than 30 missense mutations in the BTK SH2 domain
have been described in patients with XLA, and the
effects of these mutations have been analyzed in a
large number of in vitro and in vivo studies [45]. About
20 mutations affect residues directly involved in ligand
binding, presumably abolishing the interaction with
signaling partners. The remaining mutations alter
amino acids located outside the ligand-binding pocket
and reduce protein stability.
The two patients with the R335W mutation had
negligible levels of NKT cells. This suggests that NKT
cells protect against increased susceptibility to EBV
infection, EBV-positive B-cell proliferation and Hodg-
kin’s lymphoma. It has been postulated that NKT cells
play a critical role in the immune response to EBV
infection in humans [46,47]. Accordingly, the patient’s
parents, who were heterozygous for this mutation, had
low, but still detectable, numbers of NKT cells, and
did not succumb to severe EBV infection. In mice, it
has also been shown that NKT cells play important

transcription is suppressed by ITK [35,51]. Another
important transcriptional regulator is promyelocytic
leukemia zinc finger protein, which is essential for
NKT cell development and also plays a direct role in
the generation of innate T cells with a memory pheno-
type [54,55]. Additional patients with other mutations
were recently presented at the XIVth Meeting of the
European Society for Immunodeficiencies, where Huck
TEC kinases and disease A. Hussain et al.
2004 FEBS Journal 278 (2011) 2001–2010 ª 2011 The Authors Journal compilation ª 2011 FEBS
et al. [56] reported two new missense mutations and
one family with a deletion in the ITK gene. EBV-asso-
ciated lymphoproliferative disease was observed in
patients with concomitant fever, lymphadenopathy,
leukopenia and reduced numbers of NKT cells.
ITK – a potential target for HIV drug
development
It is believed that 30 million people worldwide are cur-
rently infected with the virus that causes AIDS.
Despite intensive scientific research over the past
27 years, HIV remains defiant and poses a serious
challenge to public health [57]. Although the introduc-
tion of powerful drugs has considerably improved the
quality of life for patients with AIDS in industrialized
countries, there is, at present, no definitive cure or vac-
cine. Therefore, the development of novel antiviral
drugs should be a priority. Notably, the tools of mod-
ern molecular biology have enabled the design of
nucleic acid analogs that could modulate gene expres-
sion in mammalian cells. Small interfering RNA is a

proteasome inhibitors on HIV infection and ⁄ or replica-
tion. To determine whether the depletion of ITK could
affect HIV replication, we treated activated periph-
eral blood mononuclear cells with the clinically
approved proteasome inhibitor bortezomib (Velcade)
and challenged the cells with a strain of HIV. Surpris-
ingly, HIV replication was dramatically blocked [63].
Although other reasons could not be excluded, the
overall reduction of ITK might be responsible for the
potent viral inhibition. Moreover, novel proteasome
inhibitors that are less toxic and more specific are cur-
rently in the pipeline for clinical approval [64], and
several ITK-specific inhibitors have been developed
[33,34].
Transforming activity of the ITK–SYK
fusion protein
Under physiological growth conditions, SYK seems to
be autoinhibited and is believed to exist in a closed
conformation [65–67]. Following cellular stimulation,
SYK becomes phosphorylated by an SRC family
kinase and binds to the immunoreceptor tyrosine-
based activation motifs at the inner surface of the
plasma membrane. Binding to immunoreceptor tyro-
sine-based activation motifs fixes the molecule in an
extended configuration, thereby stabilizing the nonin-
hibited state. Additional phosphorylation events
involving multiple tyrosines, in particular those at the
carboxyl terminal tail, facilitate the interaction of SYK
with the adapter proteins BLNK (also known as SLP-
65) and SLP-76, making it fully active.

and others have demonstrated that the activation and
plasma membrane localization of the fusion construct
are dependent on phosphatidylinositol 3-kinase signal-
ing, and that ITK–SYK phosphorylates the adapter
proteins SLP-76 and BLNK in the absence of external
stimuli [70–72].
More recently, a transgenic mouse expressing the
ITK–SYK fusion under the control of a T-cell-specific
promoter [72], as well as another mouse model in
which bone marrow cells were transduced with a vec-
tor expressing ITK–SYK [73], have been described.
Expression of the chimera resulted in the formation of
highly malignant peripheral T-cell lymphomas in mice,
with a phenotype resembling that described in human
patients. In T cells from transgenic mice, the ITK–
SYK fusion was found to translocate to lipid rafts and
was able to constitutively phosphorylate T-cell recep-
tor-associated signaling proteins. It is noteworthy that,
when the same fusion construct was specifically
expressed in the B-cell lineage of these animals, it did
not induce the formation of B-cell lymphomas. Thus,
transgenic mice with a CD19 promoter-mediated
expression of ITK–SYK failed to develop B-cell lym-
phoma but, instead, yielded T-cell tumors, albeit with
considerable delay, probably caused by promoter leaki-
ness [72]. Unexpectedly, in the transduced model, the
R29C mutant (corresponding to BTK R28C), which
lacks the membrane-targeting ability, showed enhanced
tumorigenicity. These findings underline the surpris-
ingly stark differences between B and T lymphocytes

external stimulation. Moreover, BTK–SYK also
showed similar phosphorylation when expressed at lev-
els comparable with those of endogenous SYK in
293T cells. The kinase-deficient versions of the fusion
proteins were not readily phosphorylated in either cell
type.
In particular, the phosphorylation, but also the total
protein level, of BTK–SYK was less than that of ITK–
SYK in 293T relative to COS7 cells. 293T cells express
endogenous SYK, but we do not know whether this
kinase influences the behavior of the fusion proteins. It
is also possible that the differential expression of SRC
family members in these two cell types may influence
the phosphorylation levels of BTK–SYK. ITK–SYK
was highly phosphorylated in both COS7 and 293T
cells and did not vary like BTK–SYK; therefore, the
differences in the PH–TH domains remain the decisive
factor for this variation.
The B-cell adapter protein BLNK (SLP-65) and its
T-cell counterpart SLP-76 are key signaling compo-
nents downstream of immunoreceptors. ITK–SYK has
been reported to potently phosphorylate SLP-76 in the
steady state [71,72]. Coexpression of BLNK or SLP-76
with BTK–SYK or ITK–SYK resulted in robust phos-
phorylation of the two adapter molecules in 293T cells.
The phosphorylation levels of BLNK and SLP-76 in
cells transfected with BTK–SYK were, however, lower
relative to ITK–SYK, consistent with the reduced
phosphorylation level of BTK–SYK itself in these
cells. In COS7 cells, where BTK–SYK and ITK–SYK

¨
liaho, Uni-
versity of Tampere, Finland, for modifications to
Fig. 1. Dara K. Mohammad was a recipient of a PhD
Fellowship from the Ministry of Higher Education and
Scientific Research ⁄ KRG-Erbil, Iraq.
References
1 Ortutay C, Nore BF, Vihinen M & Smith CI (2008)
Phylogeny of Tec family kinases: identification of a
premetazoan origin of Btk, Bmx, Itk, Tec, Txk, and the
Btk regulator SH3BP5. Adv Genet 64, 51–80.
2 Hamada N, Backesjo CM, Smith CI & Yamamoto D
(2005) Functional replacement of Drosophila Btk29A
with human Btk in male genital development and
survival. FEBS Lett 579, 4131–4137.
3 Andreotti AH, Schwartzberg PL, Joseph RE & Berg LJ
(2010) T-cell signaling regulated by the Tec family
kinase, Itk. Cold Spring Harb Perspect Biol
doi:10.1101/cshperspect.a002287.
4 Koprulu AD & Ellmeier W (2009) The role of Tec
family kinases in mononuclear phagocytes. Crit Rev
Immunol 29, 317–333.
5 Mohamed AJ, Yu L, Backesjo CM, Vargas L, Faryal
R, Aints A, Christensson B, Berglof A, Vihinen M,
Nore BF et al. (2009) Bruton’s tyrosine kinase (Btk):
function, regulation, and transformation with special
emphasis on the PH domain. Immunol Rev 228, 58–73.
6 Readinger JA, Mueller KL, Venegas AM, Horai R &
Schwartzberg PL (2009) Tec kinases regulate T-lympho-
cyte development and function: new insights into the

13 Vihinen M, Belohradsky BH, Haire RN, Holinski-Feder
E, Kwan SP, Lappalainen I, Lehvaslaiho H, Lester T,
Meindl A, Ochs HD et al. (1997) BTKbase, mutation
database for X-linked agammaglobulinemia (XLA).
Nucleic Acids Res 25, 166–171.
14 Ellmeier W, Jung S, Sunshine MJ, Hatam F, Xu Y,
Baltimore D, Mano H & Littman DR (2000) Severe
B cell deficiency in mice lacking the tec kinase family
members Tec and Btk. J Exp Med 192, 1611–1624.
15 Salim K, Bottomley MJ, Querfurth E, Zvelebil MJ,
Gout I, Scaife R, Margolis RL, Gigg R, Smith CI,
Driscoll PC et al. (1996) Distinct specificity in the
recognition of phosphoinositides by the pleckstrin
homology domains of dynamin and Bruton’s tyrosine
kinase. EMBO J 15
, 6241–6250.
16 Franke TF, Kaplan DR, Cantley LC & Toker A (1997)
Direct regulation of the Akt proto-oncogene product by
phosphatidylinositol-3,4-bisphosphate. Science 275 ,
665–668.
17 Sable CL, Filippa N, Filloux C, Hemmings BA &
Van Obberghen E (1998) Involvement of the pleckstrin
homology domain in the insulin-stimulated activation
of protein kinase B. J Biol Chem 273, 29600–29606.
18 Vihinen M, Nore BF, Mattsson PT, Backesjo CM, Nars
M, Koutaniemi S, Watanabe C, Lester T, Jones A,
Ochs HD et al. (1997) Missense mutations affecting a
conserved cysteine pair in the TH domain of Btk. FEBS
Lett 413, 205–210.
19 Valiaho J, Smith CI & Vihinen M (2006) BTKbase: the

25 Wood PM, Mayne A, Joyce H, Smith CI, Granoff DM
& Kumararatne DS (2001) A mutation in Bruton’s
tyrosine kinase as a cause of selective anti-polysaccha-
ride antibody deficiency. J Pediatr 139, 148–151.
26 Ochs HD & Smith CI (1996) X-linked agammaglobulin-
emia. A clinical and molecular analysis. Medicine
(Baltimore) 75, 287–299.
27 Plebani A, Soresina A, Rondelli R, Amato GM, Azzari
C, Cardinale F, Cazzola G, Consolini R, De Mattia D,
Dell’Erba G et al. (2002) Clinical, immunological, and
molecular analysis in a large cohort of patients with
X-linked agammaglobulinemia: an Italian multicenter
study. Clin Immunol 104, 221–230.
28 Ellmeier W, Abramova A & Schebesta A (2011) Tec
family kinases: regulation of FcepsilonRI-mediated
mast cell activation. FEBS J 278, 1990–2000.
29 Quartier P, Debre M, De Blic J, de Sauverzac R, Say-
egh N, Jabado N, Haddad E, Blanche S, Casanova JL,
Smith CI et al. (1999) Early and prolonged intravenous
immunoglobulin replacement therapy in childhood
agammaglobulinemia: a retrospective survey of 31
patients. J Pediatr 134, 589–596.
30 Gardulf A, Andersen V, Bjorkander J, Ericson D,
Froland SS, Gustafson R, Hammarstrom L, Jacobsen
MB, Jonsson E, Moller G et al. (1995) Subcutaneous
immunoglobulin replacement in patients with primary
antibody deficiencies: safety and costs. Lancet 345,
365–369.
31 Misbah S, Sturzenegger MH, Borte M, Shapiro RS,
Wasserman RL, Berger M & Ochs HD (2009) Subcuta-

5056–5063.
39 Matsumoto Y, Oshida T, Obayashi I, Imai Y, Matsui
K, Yoshida NL, Nagata N, Ogawa K, Obayashi M,
Kashiwabara T et al. (2002) Identification of highly
expressed genes in peripheral blood T cells from
patients with atopic dermatitis. Int Arch Allergy
Immunol 129, 327–340.
40 Gomez-Rodriguez J, Kraus ZJ & Schwartzberg PL
(2011) Tec family kinases Itk and Rlk ⁄ Txk in T lym-
phocytes: cross-regulation of cytokine production and
T cell fates. FEBS J 278, 1980–1989.
41 Qi Q, Kannan AK & August A (2011) Tec family
kinases: Itk signaling and the development of NKT
alphabeta and gammadelta T cells. FEBS J 278,
1970–1979.
42 Stepensky P, Weintraub M, Yanir A, Revel-Vilk S,
Krux F, Huck K, Linka RM, Shaag A, Elpeleg O,
Borkhardt A et al. (2011) IL-2-inducible T-cell kinase
deficiency: clinical presentation and therapeutic
approach. Haematologica 96, 472–476.
43 Joseph RE, Min L & Andreotti AH (2007) The linker
between SH2 and kinase domains positively regulates
catalysis of the Tec family kinases. Biochemistry 46,
5455–5462.
TEC kinases and disease A. Hussain et al.
2008 FEBS Journal 278 (2011) 2001–2010 ª 2011 The Authors Journal compilation ª 2011 FEBS
44 Guo S, Wahl MI & Witte ON (2006) Mutational analy-
sis of the SH2-kinase linker region of Bruton’s tyrosine
kinase defines alternative modes of regulation for cyto-
plasmic tyrosine kinase families. Int Immunol 18, 79–87.

T cell lineages in mice deficient for the Tec kinases Itk
and Rlk. Immunity 25, 93–104.
53 Blomberg KE, Boucheron N, Lindvall JM, Yu L,
Raberger J, Berglof A, Ellmeier W & Smith CE (2009)
Transcriptional signatures of Itk-deficient CD3+,
CD4+ and CD8+ T-cells. BMC Genomics 10, 233.
54 Raberger J, Schebesta A, Sakaguchi S, Boucheron N,
Blomberg KE, Berglof A, Kolbe T, Smith CI, Rulicke
T & Ellmeier W (2008) The transcriptional regulator
PLZF induces the development of CD44 high memory
phenotype T cells. Proc Natl Acad Sci USA 105,
17919–17924.
55 Weinreich MA, Odumade OA, Jameson SC & Hogquist
KA (2010) T cells expressing the transcription factor
PLZF regulate the development of memory-like CD8+
T cells. Nat Immunol 11, 709–716.
56 Huck K, Feyen O, Ruschendorf F, Knapp S, Niehues
T, Synaeve C, Latour S, Vettenranta K, Risse SL, Krux
F et al. (2010) A novel immunodeficiency due to muta-
tions in ITK causes an EBV-associated lymphoprolifer-
ative disease in children. In XIVth Meeting of the
European Society for Immunodeficiencies (Casanova JL
& Kutukculer N, eds), p 56. Topkon Congress Services,
Kadikoy-Istanbul, Turkey.
57 Piot P, Bartos M, Ghys PD, Walker N & Schwartland-
er B (2001) The global impact of HIV ⁄ AIDS. Nature
410, 968–973.
58 Elbashir SM, Harborth J, Lendeckel W, Yalcin A,
Weber K & Tuschl T (2001) Duplexes of 21-nucleotide
RNAs mediate RNA interference in cultured mamma-

responses. Nat Rev Immunol 9, 465–479.
67 Mocsai A, Ruland J & Tybulewicz VL (2010) The SYK
tyrosine kinase: a crucial player in diverse biological
functions. Nat Rev Immunol 10, 387–402.
68 Kuno Y, Abe A, Emi N, Iida M, Yokozawa T, Towa-
tari M, Tanimoto M & Saito H (2001) Constitutive
kinase activation of the TEL–Syk fusion gene in myelo-
dysplastic syndrome with t(9;12)(q22;p12). Blood 97,
1050–1055.
69 Streubel B, Vinatzer U, Willheim M, Raderer M &
Chott A (2006) Novel t(5;9)(q33;q22) fuses ITK to
SYK in unspecified peripheral T-cell lymphoma. Leuke-
mia 20, 313–318.
70 Rigby S, Huang Y, Streubel B, Chott A, Du MQ,
Turner SD & Bacon CM (2009) The lymphoma-associ-
ated fusion tyrosine kinase ITK–SYK requires pleck-
A. Hussain et al. TEC kinases and disease
FEBS Journal 278 (2011) 2001–2010 ª 2011 The Authors Journal compilation ª 2011 FEBS 2009
strin homology domain-mediated membrane localiza-
tion for activation and cellular transformation. J Biol
Chem 284, 26871–26881.
71 Hussain A, Faryal R, Nore BF, Mohamed AJ & Smith
CI (2009) Phosphatidylinositol-3-kinase-dependent
phosphorylation of SLP-76 by the lymphoma-associated
ITK–SYK fusion-protein. Biochem Biophys Res
Commun 390, 892–896.
72 Pechloff K, Holch J, Ferch U, Schweneker M, Brunner
K, Kremer M, Sparwasser T, Quintanilla-Martinez L,
Zimber-Strobl U, Streubel B et al. (2010) The fusion
kinase ITK–SYK mimics a T cell receptor signal and